Jump to content


Treatment Resistant Depression/anxiety

  • Please log in to reply
4 replies to this topic

#1 fishinghat


    Site Partners

  • Active Members
  • PipPipPipPipPipPipPipPipPipPipPipPipPipPipPipPipPipPip
  • 12,311 posts
  • LocationMissouri

Posted 02 July 2017 - 08:15 AM

List of approved antidepressant drugs

Anafranil (clomipramine)
Aventyl (nortriptyline)
Desyrel (trazodone HCl)
Emsam (selegiline)
Etrafon (perphenazine/amitriptyline)
Lexapro (escitalopram oxalate)
Limbitrol (chlordiazepoxide/amitriptyline)
Ludiomil (maprotiline)
Marplan (isocarboxazid)
Nardil (phenelzine sulfate)
nefazodone HCl
Norpramin (desipramine HCl)
Pamelor (nortriptyline)
Parnate (tranylcypromine sulfate)
Pexeva (paroxetine mesylate)
Remeron (mirtazapine)
Sarafem (fluoxetine HCl)
Seroquel (quetiapine)
Sinequan (doxepin)
Surmontil (trimipramine)
Symbyax (olanzapine/fluoxetine)
Tofranil (imipramine)
Tofranil-PM (imipramine pamoate)
Triavil (perphenazine/amitriptyline)
Vivactil (protriptyline)
Wellbutrin (bupropion HCl)
Zyban (bupropion HCl)

The drug Brintellix has been recently approved to treat depression, the U.S. Food and Drug Administration.

Definitions -
Agonist drugs mimic the effects of neurotransmitters naturally found in the human brain.

Antagonist Drugs
In contrast to agonist drugs which bind to the neurotransmitters in the brain, antagonist drugs do the opposite: they block the brain’s neurotransmitters.

Antidepressants and their mechanisms.

SSRIs (Selective serotonin reuptake inhibitors) controls Serotonin levels with weak control over norepinephrine and dopamine. These include:
· Zoloft (sertraline HCl)
· Fluoxetine (Prozac, Sarafem) does not appreciably inhibit and reuptake at therapeutic doses. Fluoxetine increases the concentration of circulating , a potent controller of GABA,
· Citalopram (Celexa)
· Lexapro (escitalopram oxalate) escitalopram, of all ssri on the market has the highest selectivity for the (SERT) compared to the (NET),
· Paxil (paroxetine HCl) (Pexeva, Brisdelle) is the most potent and one of the most specific selective reuptake inhibitors .Paroxetine also inhibits the reuptake of to a lesser extent (<50 nmol/L).
· Fluvoxamine (Luvox) has a 100-fold affinity for the over the . It has negligible affinity for the or any other site.

SNRI Serotonin–norepinephrine reuptake inhibitors
SNRIs are potent inhibitors of the reuptake of serotonin and norepinephrine.
· desvenlafaxine (Pristiq, Khedezla) - is a synthetic form of the major active component of venlafaxine (Effexor). It is approximately 10 times more potent at inhibiting serotonin uptake than norepinephrine.
· Cymbalta (duloxetine) - a selective neurotransmitter reuptake inhibitor for serotonin, norepinephrine, and to a lesser degree dopamine. Duloxetine increases dopamine (DA) specifically in the prefrontal cortex, where there are few DA reuptake pumps.
· levomilnacipran (Fetzima) differ from other SNRI in that they are much more balanced reuptake inhibitors of serotonin and norepinephrine. To demonstrate, the serotonin:norepinephrine ratios of SNRIs are as follows: venlafaxine= 30:1, duloxetine = 10:1, desvenlafaxine = 10:1, and levomilnacipran = 1:2.
· Effexor (venlafaxine HCl)-A comparative meta-analysis of 12 major antidepressants found that venlafaxine, mirtazapine, escitalopram, and sertraline were significantly more efficacious than duloxetine, fluoxetine, fluvoxamiine, paeoxetine, and reboxetine. A combination of venlafaxine and mirtazapine achieved remission rates of 58% in one controlled trial. In combination with an antipsychotic medicine aripiprazole, better results in treatment resistant depression in older adults have been demonstrated.

TCAs (Tricyclic antidepressants) act primarily as serotonin-norepinephrine reuptake inhibitor (SNRIs) by blocking the serotonin and norepinephrine transporters.
· Elavil (amitriptyline) Its exact mechanism of action is unclear.
Amitriptyline has strong actions on the serotonin tranbsporter and moderate effects on the norepinephrine transporter. It has negligible influence on the dopamine transporter and therefore does not affect dopamine reuptake, being nearly 1,000 times weaker on it than on serotonin.
· Asendin (amoxapine) is a moderate and strong reuptake inhibitor of seratonin and norepinephrine respectively. It has weak but negligible affinity for the dopamine transporter and GABA receptors and no affinity for the beta-adrenergic receptors.
· clomipramine (Anafranil) withdrawal can be severe. Clomipramine is a highly selective (~200x over norepinephrine) inhibitor of serotonin reuptake. It is also an antagonist/inverse agonist at the histamine H1 receptor, and the alpha1 adrenergic receptor.
· desipramine (Norpramin) It inhibits the reuptake of norepinephrine and to a minor extent serotonin.
· Doxepin is a reuptake inhibitor of serotonin and norepinephrine and acts as an antagonist of various serotonin, adrenergic, muscarinic, dopamine, and histamine receptors.
· imipramine (Tofranil) affects numerous neurotransmitter systems known to be involved in the etiology of depression, anxiety, ADHD, enuresis and numerous other mental and physical conditions. The mechanisms of imipramine's medicinal action include, but are not limited to, effects on:

           Serotonin (5-HT): very strong reuptake inhibition.
           Norepinephrine (NE): strong reuptake inhibition. Desipramine has more affinity to NET than
           Dopamine (DA): Imipramine blocks D2 receptors. Imipramine, and its metabolite desipramine,
           have no appreciable affinity for the dopamine transporter (8,500 and >10,000 KinM
           Acetylcholine (ACh): imipramine is an anticholinergic. Thus, it is prescribed with caution to the
           elderly and with extreme caution to those with psychosis, as the general brain activity
           enhancement in combination with the "dementing" effects of anticholinergics increases the
           potential of imipramine to cause hallucinations, confusion and delirium in this population.
           Imipramine is an antagonist at M2 muscarinic acetylcholine receptors (see external links).
           Epinephrine: imipramine antagonizes adreno-receptors (II), thus sometimes causing increased
           heart rate (contributed to by other effects as well), orthostatic hypotension, and a general     
           decrease in the responsiveness of the central nervous system (hence, a contribution to its
           potent anti-anxiety properties).
           σ Receptor : Activity on σ-receptors is present, but it is very low (Ki of 520 nM on σ-receptors,
           see references) and it is about half the power of amitryptiline (300 nM).
           Histamine: imipramine is an antagonist at histamine H1 receptors.
           BDNF: Which is implicated in neurogenesis in the hippocampus, and studies suggest that
           depressed patients have decreased levels of BDNF and reduced hippocampal neurogenesis.
           It is not clear how neurogenesis restores mood, as ablation of hippocampal neurogenesis in
           murine models do not show anxiety related or depression related behaviours. Chronic
           imipramine administration results in increased histone acetylation (which is associated with
           transcriptional activation and decondensed chromatin) at the hippocampal BDNF promotor,
           and also reduced expression of hippocampal

· nortriptyline (Pamelor) Effects 18 different neurotransmitter mechanisms.In one study of long-term efficacy, nortriptyline showed a higher relapse rate in comparison with phenelzine in individuals being treated for depression. Nortriptyline is an active metabolite of amitriptyline by demethylation in the liver.
· protriptyline is unique among the TCAs, protriptyline tends to be energizing instead of sedating, and is sometimes used for narcolepsy to achieve a wakefullness- promoting effect. Protriptyline increases the concentration of norepinephrine and serotonin (both chemicals that stimulate nerve cells) and, to a lesser extent, blocks the action of another brain chemical, acetylcholine.
· trimipramine (Surmontil) differs from other TCAs. It is a weak to moderate reuptake inhibitor of serotonin, and an extremely weak inhibitor of norepinephrine and dopamine reuptake. Its main effects are due to considerable receptor antagonism as follows:
Very strong: Histamine1 receptor
Strong: Seratonin 2A and alpha1 adrenergic receptors
Moderate: Dopamine2 and acetylcholine receptors
Weak: Seratonin 2C, Dopamine1 and alpha2 adrenergic receptors
Tetracyclic antidepressant
· Maprotiline It is a weak to moderate reuptake inhibitor of serotonin , and an extremely weak inhibitor of norepinephrine and dopamine reuptake. Its main effects are due to considerable receptor antagonism (stimulation) as follows:
Very strong: Histamine1 receptor
Strong: Seratonin 2A and alpha1 adrenergic receptors
Moderate: Dopamine2 and acetylcholine receptors
Weak: Seratonin 2C, Dopamine1 and alpha2 adrenergic receptors

Norepinephrine-Dopamine Reuptake Inhibitor (NDRI).
· Bupropion (Wellbutrin, Forfivo, Aplenzin) It is an effective antidepressant on its own, but is also popular as an add-on medication in cases of incomplete response to first-line SSRI antidepressants. In comparison to many other antidepressants, it does not cause as many side effects. Bupropion acts as a norepinephrine-dopamine reuptake inhibitor (NDRI).

Seratonin (5-HT1A) receptor antagonist
· vilazodone (Viibryd) In some ways, its activity can be conceptualized as a combination of an SSRI and buspirone. Vilazodone acts as a serotonin reuptake inhibitor and a seratonin 1a receptor partial agonist. It has negligible afinity for other seratonin receptor. It also exhibits negligible inhibitory activity at the norepinephrine and dopamine transporters.

Seratonin (5-HT2) receptor antagonists
· trazodone (Oleptro) is a seratonin antagonist and reuptake inhibitor.(SARI) Trazodone behaves as an antagonist at all of its receptor sites except seratonin 1A receptor where it acts as a partial agonist similarly to buspirone and tandospirone. It is an inhibitor of seratonin transportors (SERT), as well.

Seratonin (5-HT3) receptor antagonist
· vortioxetine (Brintellix) Vortioxetine is a so-called serotonin modulator and stimulator.
It inhibits serotonin and norepinephrine transporters, is an agonist to one serotonin receptor and a partial agonist to another while being an antagonist to 3 others. It also reacts with b1 adrenaline receptors.

MAOIs (Monoamine oxidase inhibitors )are chemicals that inhibit the activity of the monoamine oxidase enzyme family. They have a long history of use as medications prescribed for the treatment of depression. They are particularly effective in treating atypical depression. Due to their use being permanent and serious side effects and health risks these are usually reserved for severe cases of depression.
· isocarboxazid (Marplan) increase the levels of the monoamine neurotransmitters serotonin, dopamine and norepinephrine in the brain and is an irreversible MAOI.
· phenelzine (Nardil) Along with tranylcypromine and isocarboxazid, phenelzine is one of the few non-selective and irreversible MAOIs still in widespread clinical use.
· selegiline (Emsam), which comes as a transdermal patch it is a selective irreversible MAO-B inhibitor.
· tranylcypromine (Parnate) acts as a nonselective and irreversible inhibitor of monoamine oxidase. In addition, tranylcypromine functions as a norepinephrine and dopamine releasimg agent with approximately 1/10 the potency of amphetamines.
Noradrenergic antagonist
· Mirtazapine (Remeron) blocks the A2 adrenergic receptors (enhancing norepinephrine release), and selectively antagonizes the seratonin 2 receptors in the central and peripheral nervous system. It also enhances serotonin neurotransmission at the seratonin 1 receptor and blocks the histamine1receptors.

Natural antidepressants

· St. John's wort
However St. John’s wort is a risky herb with many side effects and negative interactions.
Its side effects are surprisingly similar to those of antidepressants including anxiety, panic attacks, dizziness, nausea and spikes in blood pressure.
It can make dementia worse and trigger psychosis or mania in bipolar disorder patients.
It can make your birth control pills less effective.
Positive effects in neurotransmitter regulation (in beta adrenergic systems and glutamate receptors) and ion channel conductance

· S-adenosyl-L-methionine (SAMe) - SAMe is made in the body from a reaction between methionine, which is an essential amino acid, and adenosine triphosphate, a molecule that carries energy. SAMe is involved in many different reactions in the body.
SAMe has been used to treat psychiatric illnesses, infertility, liver problems, premenstrual disorders, and musculoskeletal conditions.
SAMe has been widely studied for osteoarthritis and depression. There is evidence that SAMe may help reduce the pain of osteoarthritis.
Mechanism is not understood.

· Curcumin - Shown to be as effective as Prozac. Proposed mechanism. include:
Monoamine oxidase (MAO) inhibitory property of curcumin
Modulating the serotonin and dopamine neurotransmission in brain
Increasing the levels of neurotrophic factors, particularly brain derived neurotrophic factor (BDNF)
Antiinflammatory and antioxidant property

· Saffron -Shown to be as effective as Prozac. Saffron's antidepressant effects potentially are due to its serotonergic, antioxidant, anti-inflammatory, neuro-endocrine and neuroprotective effects.

· Tryptophan -It is essential in humans, meaning the body cannot synthesize it and thus it must be obtained from the diet. Tryptophan is also a precursor to the neurotransmitter serotonin and the hormone melatonin. This leads to its usefullness in controlling depression.

· EGCG (Epigallocatechin gallate) a type of natural plant phenol and antioxidant. Helps regulate the HPA axis.

· Acetyl-l-Carnitine -Acetyl-L-carnitine, ALCAR or ALC, is an acelylated form of L-carbitine. It is naturally produced by the body, although it is often taken as a dietary supplement. Acetylcarnitine is broken down in the blood by plasma esterases to carnitine which is used by the body to transport fatty acids into the mitochondria for breakdown. Animal and cellular models suggest that ALC's neuroplasiticity effect, membrane modulation, and neurotransmitter regulation may play an important role in treatment of depression. Carnitine is important in the -oxidation of fatty acids and the acetyl form can be used to maintain acetyl-CoA levels. Other reported neurobiological effects of ALCAR include modulation of: (1) brain energy and phospholipid metabolism; (2) cellular macromolecules, including neurotrophic factors and neurohormones; (3) synaptic morphology; and (4) synaptic transmission of multiple neurotransmitters. Potential molecular mechanisms of ALCAR activity include: (1) acetylation of -NH2 and -OH functional groups in amino acids and N terminal amino acids in peptides and proteins resulting in modification of their structure, dynamics, function and turnover; and (2) acting as a molecular chaperone to larger molecules resulting in a change in the structure, molecular dynamics, and function of the larger molecule.

· Kava -The mechanisms of action proposed for kava kava include decreased levels of glutamate, an excitatory neurotransmitter, activation of dopaminergic neurons, interaction with GABA receptors, direct action on muscles leading to relaxation, elevation of dopamine and serotonin levels via inhibition of monoamine uptake, and cellular actions similar to mood stabilizers.

· Arctic Root - Rhodiola root extract improves the activities of dopamine and serotonin in the brain by blocking the enzymatic breakdown of these brain chemicals by monoamine oxidases.
In addition, Rhodiola root extract promotes the transport of dopamine and serotonin precursors into the brain by increasing the permeability of the blood brain barrier to these precursors.
Some studies have shown that serotonin levels in the brain can be boosted by as much as 30% with the use of rhodiola root extract. This increase is due to the combination of the two mechanisms stated above.

#2 fishinghat


    Site Partners

  • Active Members
  • PipPipPipPipPipPipPipPipPipPipPipPipPipPipPipPipPipPip
  • 12,311 posts
  • LocationMissouri

Posted 02 July 2017 - 08:46 AM

There are litgerally over 100 major and minor side effects for each of the pharmaceutical antidepressants. In addition there are over 50 Black Box warnings (the most serious) that have been issued by the FDA. In short, there are NO safe antidepressants.

Natural antidepressants

· St. John's wort
Special Precautions & Warnings:
Pregnancy and breast-feeding: St. John's wort is POSSIBLY UNSAFE when taken by mouth during pregnancy. There is some evidence that it can cause birth defects in unborn rats. No one yet knows whether it has the same effect in unborn humans. Nursing infants of mothers who take St. John's wort can experience colic, drowsiness, and listlessness. Until more is known, do not use St. John's wort if you are pregnant or breast-feeding.

Children: St. John's work is POSSIBLY SAFE when taken by mouth for up to 8 weeks in children 6-17 years-old.

Alzheimer's disease: There is concern that St. John's wort might contribute to dementia in people with Alzheimer's disease.

Anesthesia: Use of anesthesia in people who have used St. John's wort for 6 months may lead to serious heart complications during surgery. Stop using St. John's wort at least 2 weeks before a scheduled surgery.

Attention deficit-hyperactivity disorder (ADHD): There is some concern that St. John's wort might worsen symptoms of ADHD, especially in people taking the medication methylphenidate for ADHD. Until more is known, don't use St. John's wort if you are taking methylphenidate.

Bipolar disorder: People with bipolar disorder cycle between depression and mania, a state marked by excessive physical activity and impulsive behavior. St. John's wort can bring on mania in these individuals and can also speed up the cycling between depression and mania.

Depression: In people with major depression, St. John's wort might bring on mania, a state marked by excessive physical activity and impulsive behavior.

Infertility: There are some concerns that St. John's wort might interfere with conceiving a child. If you are trying to conceive, don't use St. John's wort, especially if you have known fertility problems.

Schizophrenia: St. John's wort might bring on psychosis in some people with schizophrenia.

Surgery: St. John's wort might affect serotonin levels in the brain and as a result interfere with surgical procedures. Stop using St. John's wort at least two weeks before a scheduled surgery.

· S-adenosyl-L-methionine (SAMe) -
SAMe is LIKELY SAFE when taken by mouth, given intravenously (by IV), or when injected as a shot, appropriately. It can sometimes cause gas, vomiting, diarrhea, constipation, dry mouth, headache, mild insomnia, anorexia, sweating, dizziness, and nervousness, especially at higher doses. It can also make some people with depression feel anxious.
Special Precautions & Warnings:
Pregnancy: SAMe is POSSIBLY SAFE when given intravenously (by IV) in the short-term during the third trimester of pregnancy. An 800 mg dose of SAMe has been used intravenously for 14-20 days without any adverse effects. There is not enough reliable information about the safety of taking higher doses of SAMe for longer periods of time or during the earlier trimesters of pregnancy. Stay on the safe side and avoid use.

Breast-feeding: There is not enough reliable information about the safety of taking SAMe if you are pregnant or breast feeding. Stay on the safe side and avoid use.

Children: SAMe is POSSIBLY SAFE when taken by mouth or used intravenously (by IV) in children in the short-term.

Bipolar disorder: Use of SAMe can cause people with bipolar disorder to convert from depression to mania.

Inherited disorder called Lesch-Nyhan syndrome: SAMe might make symptoms of Lesch-Nyhan syndrome worse.

Parkinson's disease: SAMe might make Parkinson's symptoms worse.

Surgery: SAMe might affect the central nervous system. This could interfere with surgery. Stop taking SAMe at least 2 weeks before a scheduled surgery.

· Curcumin -
Turmeric is LIKELY SAFE when taken by mouth or applied to the skin appropriately for up to 8 months.

Turmeric is POSSIBLY SAFE when it is used as an enema or a mouthwash in the short-term.

Turmeric usually does not cause significant side effects; however, some people can experience stomach upset, nausea, dizziness, or diarrhea.

In one report, a person who took very high amounts of turmeric, over 1500 mg twice daily, experienced a dangerous abnormal heart rhythm. However, it is unclear if turmeric was the actual cause of this side effect. Until more is known, avoid taking excessively large doses of turmeric.
Special Precautions & Warnings:
Pregnancy and breast-feeding: During pregnancy and while breast-feeding, turmeric is LIKELY SAFE when taken by mouth in amounts commonly found in food. However, turmeric is LIKELY UNSAFE when taken by mouth in medicinal amounts during pregnancy. It might promote a menstrual period or stimulate the uterus, putting the pregnancy at risk. Do not take medicinal amounts of turmeric if you are pregnant. There is not enough information to rate the safety of medicinal amounts of turmeric during breast-feeding. It is best not to use it.

Gallbladder problems: Turmeric can make gallbladder problems worse. Do not use turmeric if you have gallstones or a bile duct obstruction.

Bleeding problems: Taking turmeric might slow blood clotting. This might increase the risk of bruising and bleeding in people with bleeding disorders.

Diabetes: Curcumin, a chemical in turmeric, might decrease blood sugar in people with diabetes. Use with caution in people with diabetes as it might make blood sugar too low.

A stomach disorder called gastroesophageal reflux disease (GERD): Turmeric can cause stomach upset in some people. It might make stomach problems such as GERD worse. Do not take turmeric if it worsens symptoms of GERD.

Hormone-sensitive condition such as breast cancer, uterine cancer, ovarian cancer, endometriosis, or uterine fibroids: Turmeric contains a chemical called curcumin, which might act like the hormone estrogen. In theory, turmeric might make hormone-sensitive conditions worse. However, some research shows that turmeric reduces the effects of estrogen in some hormone-sensitive cancer cells. Therefore, turmeric might have beneficial effects on hormone-sensitive conditions. Until more is known, use cautiously if you have a condition that might be made worse by exposure to hormones.

Infertility: Turmeric might lower testosterone levels and decrease sperm movement when taken by mouth by men. This might reduce fertility. Turmeric should be used cautiously by people trying to have a baby.

Iron deficiency: Taking high amounts of turmeric might prevent the absorption of iron. Turmeric should be used with caution in people with iron deficiency.

Surgery: Turmeric might slow blood clotting. It might cause extra bleeding during and after surgery. Stop using turmeric at least 2 weeks before a scheduled surgery.

· Saffron -
Saffron is POSSIBLY SAFE for most people when taken by mouth as a medicine for up to 6 weeks. Some possible side effects include dry mouth, anxiety, dizziness, drowsiness, nausea, change in appetite, and headache. Allergic reactions can occur in some people.

Taking large amounts of saffron by mouth is POSSIBLY UNSAFE. High doses can cause poisoning, including yellow appearance of the skin, eyes, and mucous membranes; vomiting; dizziness; bloody diarrhea; bleeding from the nose, lips, and eyelids; numbness; and other serious side effects. Doses of 12-20 grams can cause death.

Special Precautions & Warnings:
Pregnancy and breast-feeding: Taking saffron by mouth in amounts larger than what is normally found in food is LIKELY UNSAFE. Larger amounts of saffron can make the uterus contract and might cause a miscarriage.

Not enough is known about the safety of using saffron during breast-feeding. Stay on the safe side and avoid use.

Bipolar disorder: Saffron seems to be able to affect mood. There is a concern that it might trigger excitability and impulsive behavior (mania) in people with bipolar disorder. Don’t use saffron if you have this condition.

Allergies to Lolium, Olea (includes olive), and Salsola plant species: People who are allergic to these plants might also be allergic to saffron.

Heart conditions: Saffron might affect how fast and how strong the heart beats. Taking large amounts of saffron might worsen some heart conditions.

Low blood pressure: Saffron might lower blood pressure. Taking saffron might make blood pressure become too low in people with low blood pressure.

· Tryptophan -
L-tryptophan is POSSIBLY UNSAFE when taken by mouth. It has been linked to over 1500 reports of eosinophilia-myalgia syndrome (EMS) and 37 deaths. EMS is a neurological condition with symptoms that include fatigue; intense muscle pain; nerve pain; skin changes; baldness; rash; and pain and swelling affecting the joints, connective tissue, lungs, heart, and liver. Symptoms tend to improve over time, but some people may still experience symptoms up to 2 years after they develop EMS. Some people report that their symptoms have never gone away completely.

In 1990, L-tryptophan was recalled from the market due to these safety concerns. After the limitation of L-tryptophan products, the number of EMS cases dropped sharply. The exact cause of EMS in patients taking L-tryptophan is unknown, but some evidence suggests it may be due to contaminated L-tryptophan products. About 95% of all EMS cases were traced to L-tryptophan produced by a single manufacturer in Japan. Currently, under the Dietary Supplement Health and Education Act (DSHEA) of 1994, L-tryptophan is available and marketed as a dietary supplement.

L-tryptophan can cause some side effects such as heartburn, stomach pain, belching and gas, nausea, vomiting, diarrhea, and loss of appetite. It can also cause headache, lightheadedness, drowsiness, dry mouth, visual blurring, muscle weakness, and sexual problems.
Special Precautions & Warnings:
Pregnancy and breast-feeding: L-tryptophan is LIKELY UNSAFE in pregnancy because it may harm the unborn child. Not enough is known about the safety of L-tryptophan during breast-feeding. Avoid using L-tryptophan during pregnancy and breast-feeding.

A white blood cell disorder called eosinophilia: L-tryptophan might make this condition worse. L-tryptophan has been associated with the development of eosinophilia-myalgia syndrome (EMS).

Liver or kidney disease: L-tryptophan might make these conditions worse since it has been associated with the development of eosinophilia-myalgia syndrome (EMS).

· EGCG (Epigallocatechin gallate)
Green tea is LIKELY SAFE for most adults when consumed as a drink in moderate amounts or when green tea extract is applied to the skin as a specific ointment (Veregen, Bradley Pharmaceuticals), short-term. Green tea extract is POSSIBLY SAFE for most people when taken by mouth for up to 2 years, when applied to the skin as other ointments short-term, or when used as a mouthwash short-term. In some people, green tea can cause stomach upset and constipation. Green tea extracts have been reported to cause liver problems in rare cases.

Green tea is POSSIBLY UNSAFE when taken by mouth long-term or in high-doses. It can cause side effects because of the caffeine. These side effects can range from mild to serious and include headache, nervousness, sleep problems, vomiting, diarrhea, irritability, irregular heartbeat, tremor, heartburn, dizziness, ringing in the ears, convulsions, and confusion. Green tea seems to reduce the absorption of iron from food. Drinking very high doses of green tea is LIKELY UNSAFE and can actually be fatal. The fatal dose of caffeine in green tea is estimated to be 10-14 grams (150-200 mg per kilogram). Serious toxicity can occur at lower doses.
Special Precautions & Warnings:
Children: Green tea is POSSIBLY SAFE for children when used in amounts commonly found in foods and beverages or when used for gargling three times daily for up to 90 days.

Pregnancy and breast-feeding: If you are pregnant or breast-feeding, green tea in small amounts - about 2 cups per day - is POSSIBLY SAFE. This amount of green tea provides about 200 mg of caffeine. However, drinking more than 2 cups of green tea per day is POSSIBLY UNSAFE. Consuming more than 2 cups of green tea daily has been linked to an increased risk of miscarriage and other negative effects due to the caffeine content. Also, green tea might increase the risk of birth defects associated with folic acid deficiency. In women who are nursing, caffeine passes into breast milk and can affect a nursing infant. Don't drink an excessive amount of green tea if you are pregnant or breast-feeding.

"Tired blood" (anemia): Drinking green tea may make anemia worse.

Anxiety disorders: The caffeine in green tea might make anxiety worse.

Bleeding disorders: Caffeine in green tea might increase the risk of bleeding. Don't drink green tea if you have a bleeding disorder.

Heart conditions: Caffeine in green tea might cause irregular heartbeat.
Diabetes: Caffeine in green tea might affect blood sugar control. If you drink green tea and have diabetes, monitor your blood sugar carefully.

Diarrhea: Green tea contains caffeine. The caffeine in green tea, especially when taken in large amounts, can worsen diarrhea.

Glaucoma: Drinking green tea increases pressure inside the eye. The increase occurs within 30 minutes and lasts for at least 90 minutes.

High blood pressure: The caffeine in green tea might increase blood pressure in people with high blood pressure. However, this does not seem to occur in people who regularly drink green tea or other products that contain caffeine.

Irritable bowel syndrome (IBS): Green tea contains caffeine. The caffeine in green tea, especially when taken in large amounts, can worsen diarrhea and might worsen symptoms of IBS.

Liver disease: Green tea extract supplements have been linked to several cases of liver damage. Green tea extracts might make liver disease worse.
Weak bones (osteoporosis): Drinking green tea can increase the amount of calcium that is flushed out in the urine. Caffeine should be limited to less than 300 mg per day (approximately 2-3 cups of green tea). It is possible to make up for some calcium loss caused by caffeine by taking calcium supplements.

· Acetyl-l-Carnitine -
Acetyl-L-carnitine is LIKELY SAFE for most adults. It can cause some side effects including stomach upset, nausea, vomiting, and restlessness. It can cause a "fishy" odor of the urine, breath, and sweat.

Special Precautions & Warnings:
Pregnancy and breast-feeding: Not enough is known about the use of acetyl-L-carnitine during pregnancy and breast-feeding. Stay on the safe side and avoid use.

Under-active thyroid (hypothyroidism): There is some concern that acetyl-L-carnitine might interfere with thyroid hormone. Don’t use acetyl-L-carnitine if you have an under-active thyroid.

Seizures: An increase in the number or seriousness of seizures has been reported in people with a history of seizures who have used L-carnitine by mouth or by IV (intravenously). Since L-carnitine is related to acetyl-L-carnitine, there is a concern that this might also occur with acetyl-L-carnitine. If you have ever had a seizure, don’t take acetyl-L-carnitine.

· Kava -
Kava is POSSIBLY UNSAFE when taken by mouth. Don't use it. Serious illness, including liver damage, has occurred even with short-term use of normal doses. The use of kava for as little as one to three months has resulted in the need for liver transplants, and even death. Early symptoms of liver damage include yellowed eyes and skin (jaundice), fatigue, and dark urine. If you decide to take kava, despite warnings to the contrary, be sure to get frequent liver function tests.

Using kava can make you unable to drive or operate machinery safely. Do not take kava before you plan on driving. "Driving-under-the-influence" citations have been issued to people driving erratically after drinking large amounts of kava tea.
Special Precautions & Warnings:
Pregnancy and breast-feeding: Don't use kava if you are pregnant or breast-feeding. Kava is POSSIBLY UNSAFE when taken by mouth. There is a concern that it might affect the uterus. Also, some of the dangerous chemicals in kava can pass into breast milk and might hurt a breast-fed infant.

Depression: Kava use might make depression worse.

Liver problems: Kava can cause liver problems even in healthy people. Taking kava if you already have liver disease is taking a risk. People with a history of liver problems should avoid kava.
Parkinson's disease: Kava might make Parkinson's disease worse. Do not take kava if you have this condition.

Surgery: Kava affects the central nervous system. It might increase the effects of anesthesia and other medications used during and after surgery. Stop using kava at least 2 weeks before a scheduled surgery.
The FDA has set up special regulations and warnings on the use of Kava.

· Arctic Root -
Rhodiola is POSSIBLY SAFE when taken by mouth, short-term (for up to 6-10 weeks). The safety of long-term use is not known. The potential side effects of rhodiola are not known.
Special Precautions & Warnings:
Pregnancy and breast-feeding: There isn’t enough reliable information about the safety of taking Rhodiola if you are pregnant or breast feeding. Stay on the safe side and avoid use.
Dangers of Rhodiola Rosea, also called Arctic Root, Golden Root
Folks are commonly encouraged to increase their dose of rhodiola until they achieve the desired effect. Many sources claim it is a safe herb with very little side effects. Most common side effects are difficulty sleeping, drowsiness, gastrointestinal distress, headache, and dizziness. Increasing the dose of anything until you achieve the desired effect is a dangerous practice for any botanical and should be avoided.
Reported Side Effects on Patients Taking Rhodiola
These side effects usually occur when you are on a higher dosage and when you take it with caffeine. So let’s say you are a coffee drinker. You are at increased risk. If you are a Coca Cola or Pepsi lover, symptoms may worsen. Any stimulant product or new weight loss products that contain caffeine will worsen the symptoms of the following:
⦁ Anxiety and agitation
⦁ Nauseous
⦁ Restlessness
⦁ Insomnia
⦁ Hypersalivation
Pregnancy and Breastfeeding
There is not enough research to prove that rhodiola is safe for pregnant women or women who are breastfeeding.
Rhodiola may lower blood sugar levels. If patients are taking a medication to lower blood glucose it could make their levels go dangerously low. And if their levels go too low and blood sugars bottom out, they can pass out. The consequences of low blood glucose can be just as dangerous as high blood sugar.
Blood Pressure
Rhodiola may alter blood pressure and is not recommended for patients taking ACE inhibitors. Rhodiola can also increase the risk of bleeding when it’s taken with aspirin or prescription anticoagulants such as warfarin (Coumadin®) or heparin. It is not proven safe with anti-platelet drugs such as clopidogrel (Plavix®). Rholiola should not be taken with non-steroidal anti-inflammatory drugs like ibuprofen (Motrin®, Advil®) or naproxen (Naprosyn®, Aleve®).
Autoimmune Disorders
Rhodiola can increase the symptoms of autoimmune disorders because it stimulates the immune system. Conditions such as rheumatoid arthritis, inflammatory bowel disorders (Crohn’s disease/ ulcerative colitis), neurological disorders such as multiple sclerosis, lupus, as well as autoimmune thyroid disorders such as Hashimoto’s and thyroiditis can all be exacerbated by the use of rhodiola.
Rhodiola is not proven safe for folks on thyroid medicine. It may change (lower?) thyroid levels. If you take thyroid medicine you should not take rhodiola. If your thyroid testing is irregular, please consult your physician.
A 2008 study at the UCLA Anxiety Disorders Program suggests rhodiola can aid patients diagnosed with generalized anxiety disorder (GAD). Rhodiola, however, may have stimulant-like effects and without knowing a patient’s biochemical status, rhodiola can worsen their symptoms of anxiety. Patients suffering from anxiety who also exhibit the ‘shakes’ from caffeine and ephedrine should not take rhodiola.
Bipolar Disorder
Rhodiola rosea should not be prescribed to patients with manic behavior disorders. If you have bipolar disorder, for example, rhodiola can be dangerous because it can cause mania.
Rhodiola should not be prescribed to patients with antidepressant sensitivity, either. Rhodiola rosea can cause drowsiness for patients on benzodiazepines, SSRI and SNRI antidepressants. It is not recommended for patients on SSRI medications or MAOI medication because it can cause serotonin syndrome.
Birth Control Pills
It can make your birth control pills less effective.


#3 fishinghat


    Site Partners

  • Active Members
  • PipPipPipPipPipPipPipPipPipPipPipPipPipPipPipPipPipPip
  • 12,311 posts
  • LocationMissouri

Posted 02 July 2017 - 08:57 AM

List of Anxiety Meds in order of usage, from most frequently prescribed to least frequently subscribed.

Name Availability Number of Rating of effectiveness
by users
Xanax Rx D 4 378 8.0
clonazepam Off Label Rx D 4 528 8.0
Ativan Rx D 4 230 8.0
alprazolam Rx D 4 562 8.0
lorazepam Rx D 4 419 8.0
Lexapro Rx C N 473 7.0
BuSpar Rx B N 298 6.0
Valium Rx D 4 125 8.0
buspirone Rx B N 521 6.0
hydroxyzine Rx N N 393 5.0
Cymbalta Rx C N 156 7.0
diazepam Rx D 4 254 8.0
Vistaril Rx N N 122 5.0
Effexor XR Rx C N 128 7.0
Paxil Rx D N 173 7.0
escitalopram Rx C N 651 7.0
gabapentin Off Label Rx C N 237 8.0
trazodone Off Label Rx C N 61 7.0
bupropion Off Label Rx C N 68 7.0
clonidine Off Label Rx C N 26 7.0
propranolol Off Label Rx C N 99 8.0
paroxetine Rx D N 208 7.0
Tenormin Rx D N 3 8.0
venlafaxine Rx C N 182 7.0
Alprazolam Intensol Rx D 4 3 9.0
duloxetine Rx C N 167 7.0
Librium Rx N 4 16 7.0
mirtazapine Off Label Rx C N 164 6.0
Niravam Rx D 4 10 9.0
tramadol Off Label Rx C 4 54 9.0
Tranxene Rx N 4 7 9.0
atenolol Rx D N 26 7.0
Lorazepam Intensol Rx D 4 2 7.0
Diazepam Intensol Rx D 4 3 9.0
lamotrigine Off Label Rx C N 20 6.0
Paxil CR Rx D N 7 8.0
risperidone Off Label Rx C N 23 6.0
doxepin Rx N N 12 6.0
oxazepam Rx N 4 33 9.0
chlordiazepoxide Rx N 4 19 7.0
clorazepate Rx N 4 25 8.0
Diastat Rx D 4 Add Add
Diastat AcuDial Rx D 4 Add Add
Diastat Pediatric Rx D 4 Add Add
Pexeva Rx D N 3 8.0
Sinequan Rx N N 1 5.0
Vanspar Rx B N 2 3.0
amitriptyline / perphenazine Rx N N 4 9.0
Compro Rx/OTC N N Add Add
Etrafon Rx N N 1 9.0


#4 fishinghat


    Site Partners

  • Active Members
  • PipPipPipPipPipPipPipPipPipPipPipPipPipPipPipPipPipPip
  • 12,311 posts
  • LocationMissouri

Posted 02 July 2017 - 09:01 AM

Treatment Resistant Anxiety

Encephale. 2015 Jun;41(3):260-5. doi: 10.1016/j.encep.2013.11.002. Epub 2014 Nov 14.
[Treatment-resistant anxiety disorders: A literature review of drug therapy strategies].
Ammar G1, Naja WJ1, Pelissolo A2.
Anxiety disorders are widespread psychiatric conditions with significant social and professional disability, poor quality of life, an increased risk of suicide, and frequent attendance of medical services. Serotonin reuptake inhibitors (SRI) and serotonin and norepinephrine reuptake inhibitors (SNRI) have demonstrated a rather robust efficacy for the treatment of most of anxiety disorders. Nevertheless a substantial number of patients are resistant or still suffer from residual symptoms despite this first line treatment. The objective of our paper is to review relevant studies for the pharmacologic management of anxiety disorders resistant to the first line treatment. For this purpose, we conducted a pubmed/medline search for double-blind placebo-controlled trials of treatment-resistant anxiety disorders. An adequate trial for a SRI in the treatment of obsessive-compulsive disorder (OCD) should continue for at least 12 weeks. Special considerations of the comorbidities and symptom profile could help in the choice of an appropriate pharmacotherapy. Several trials have highlighted the efficacy of antipsychotics as an add-on to SRI in treatment-resistant OCD such as haloperidol more so when comorbid with a tic disorder, or risperidone that can reduce OCD as well as depressive symptoms. Aripiprazole has been shown efficacious in two placebo-controlled double-blind trials, while the efficacy of quetiapine and olanzapine remains controversial. Other trials showed some efficacy of anticonvulsants (lamotrigine, topiramate), pindolol, memantin and N-acetylcystein as an adjunctive treatment to SRI for resistant OCD. Few trials have investigated selective serotonin reuptake inhibitors (SSRI) or SNRI resistant generalized anxiety disorder showing a failure of adjunctive therapy with olanzapine, quetiapine, ziprasidone and risperidone. These studies were underpowered and very limited in number. Adjunctive risperidone for resistant post-traumatic stress disorder (PTSD) showed benefit in some but not all trials. Olanzapine was beneficial for the reduction of the CAPS score in addition to the improvement of sleep disturbances. Furthermore, prazosin was efficacious by reducing PTSD symptoms, sleep disturbances, nightmares, and psychological distress. One double-blind placebo-controlled study was conducted to investigate treatment-resistant social phobia showing no benefit of pindolol add-on paroxetine. Our results demonstrate that the pharmacological management of treatment-resistant anxiety disorders is not sufficiently investigated in double-blind placebo-controlled trials, despite a growing evidence in favor of antipsychotics and some other pharmacological agents in resistant OCD and, to a lesser extent, PTSD. Hence, there is a crucial need for larger double-blind placebo-controlled trials for resistant anxiety disorders. Finally, being out of the scope of our review, we omitted studies of non-pharmacologic therapies.

Expert Opin Pharmacother. 2016;17(2):159-68. doi: 10.1517/14656566.2016.1109628. Epub 2015 Dec 4.
Treatment-resistant panic disorder: a systematic review.
Freire RC1, Zugliani MM1, Garcia RF1, Nardi AE1.
Author information
The prevalence of panic disorder (PD) in the population is high and these patients have work impairment, high unemployment rates, seek medical treatment more frequently and have more hospitalizations than people without panic symptoms. Despite the availability of pharmacological, psychological and combined treatments, approximately one-third of all PD patients have persistent panic attacks and other PD symptoms after treatment.
MEDLINE/Pubmed, CENTRAL, PsycINFO and Web of Science databases were searched for clinical trials in treatment-resistant PD. Only studies published between 1980 and 2015, in English, with human subjects, considered "journal articles" and clinical trial were included. We included trials recruiting only adult subjects with treatment-resistant PD, consistent with criteria from DSM-III to DSM5. We included all prospective experimental studies. Case, case series, retrospective studies or studies with <10 PD subjects were not included.
Only 11 articles were included in this review. There were few quality studies, only two were randomized, controlled and double blind. Augmentation of the pharmacological treatment with cognitive-behavioral therapy demonstrated some short-term efficacy in treatment-resistant PD. There were also preliminary evidences of efficacy for monotherapy with reboxetine and olanzapine, and augmentation with pindolol, divalproex sodium, aripiprazole and olanzapine in short-term treatment.

Int Clin Psychopharmacol. 2015 Sep;30(5):265-71. doi: 10.1097/YIC.0000000000000087.
Pregabalin for the treatment of patients with generalized anxiety disorder with inadequate treatment response to antidepressants and severe depressive symptoms.
Olivares JM1, Álvarez E, Carrasco JL, Pérez Páramo M, López-Gómez V.
Author information
To evaluate the effectiveness of pregabalin in patients with resistant generalized anxiety disorder (GAD) and severe depressive symptoms, we carried out a post-hoc analysis of a multicenter, prospective, and observational 6-month study. We included patients who were at least 18 years old, fulfilled the Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSM-IV) criteria for GAD, showed inadequate responses to previous courses of antidepressant treatment, had Montgomery-Asberg Rating Scale scores of at least 35, had not received pregabalin previously, and were prescribed pregabalin upon entry into this study. We included 1815 patients fulfilling the DSM-IV criteria for GAD, and 133 (7.3%) fulfilled the selection criteria for these analyses. Ninety-seven percent of the patients received pregabalin (mean dose: 222 mg/day) in combination with other psychotropics. The Hamilton Anxiety Scale total score was reduced by a mean of 20.3 points (95% confidence interval, 22.1-18.4) (57.2% reduction) at month 6. Pregabalin also ameliorated comorbid depressive symptoms, with a reduction in the mean score of the Montgomery-Asberg Rating Scale of 22.3 points (95% confidence interval, 24.2-20.4) (56.6% reduction). Our results suggest that pregabalin, as part of a combination regimen with antidepressants and/or benzodiazepines, might be effective for the treatment of patients with GAD who have shown inadequate response to previous antidepressants and have severe depressive symptoms.

Mol Psychiatry. 2006 Sep;11(9):805-14. Epub 2006 Jul 18.
Treatment-resistant anxiety disorders.
Bystritsky A1.
Several epidemiological studies confirmed that Anxiety Disorders as a group are the most prevalent psychiatric conditions in the United States. The importance of these conditions is underlined by the fact that they cause significant disability, poor quality of life, alcohol and drug abuse. Anxiety disorders are treatable conditions and respond to the front-line interventions such as serotonin reuptake inhibitors and cognitive behavioral therapy. However, only about 60% of patients respond to those treatments to any significant degree. Many still have residual symptoms or stay treatment refractory. The group of anxiety patients that is resistant to the treatment has been shown to have very poor quality of life and have highest rate of suicidal attempts than any other disorders. Many biological, treatment specific and social factors are affecting treatment resistance. In this paper, we are attempting to review reasons for the treatment resistance. In addition, we would like to review current strategies that could be helpful in reducing treatment resistance and aiding people chronically suffering from these severe and disabling conditions.

Cochrane Database Syst Rev. 2006 Oct 18;(4):CD005473.
Pharmacotherapy augmentation strategies in treatment-resistant anxiety disorders.
Ipser JC1, Carey P, Dhansay Y, Fakier N, Seedat S, Stein DJ.
A large proportion of patients with anxiety disorders fail to respond to first-line medication interventions, despite evidence of the effectiveness of these agents.
To assess the effects of medication versus placebo augmentation in the treatment of patients with anxiety disorders who have failed to respond adequately to first-line drug therapies.
The Cochrane Depression, Anxiety & Neurosis Group (CCDAN) specialised registers (CCDANCTR-Studies and CCDANCTR-References) were searched on 3/8/2005, MEDLINE (January 1966 to July 2005) and PsycINFO (1966 to 2005, Part A). Unpublished trials were identified through the Controlled Trials database and the National Institute of Health's Computer Retrieval of Information on Scientific Projects (CRISP) service (1972 to 2005). Additional studies in any language were sought in reference lists of retrieved articles.
All randomised controlled trials (RCTs) of the medication augmentation of pharmacotherapy for treatment resistant anxiety disorders.
Two raters independently assessed RCTs for inclusion in the review, collated trial data, and assessed trial quality. Investigators were contacted to obtain missing data. Summary statistics were stratified by class of augmentation agent and anxiety disorder. Overall effect estimates were calculated using a random-effects model, heterogeneity was assessed and subgroup/sensitivity analyses were undertaken.
Twenty eight short-term (average of seven weeks) randomised controlled trials (740 participants) were included in the review, 20 of which investigated augmentation of medication for treatment-resistant obsessive compulsive disorder (OCD). Summary statistics for responder status from nine trials demonstrate overall superiority of a variety of medication agents to placebo (relative risk of non-response (RR) 3.16, 95% CI 1.08 to 9.23). Similarly, symptom severity was significantly reduced in the medication groups, relative to placebo (number of trials (N) = 14, standardised mean difference (SMD) -0.87, 95% CI -1.37 to -0.36). There is no evidence of a difference between medication and placebo in total dropout rate, or in the number of dropouts due to adverse events.
Medication augmentation can be an effective and well-tolerated short-term treatment strategy for non-responders to first-line pharmacotherapy of anxiety disorders. However, any conclusions must be tentative in view of methodological and clinical heterogeneity, and the fact that much of the relevant database is based on antipsychotic augmentation trials in OCD patients resistant to serotonin reuptake inhibitors (SRIs). Additional data are needed to address several areas, including the efficacy of augmentation over the longer-term, and the value of medication augmentation in comparison to other strategies (e.g. switching medication, adding psychotherapy).

J Clin Psychiatry. 1993 May;54 Suppl:69-74.
Therapeutic strategies for the patient with treatment-resistant anxiety.
Coplan JD1, Tiffon L, Gorman JM.
Outcome of anxiety disorder treatment with psychotherapy and medication is generally as good as or better than that of other psychiatric illnesses. Nevertheless, refractory cases occur. The first step in approaching the treatment-resistant patient with an anxiety disorder is to be certain that the treatment has been adequate. Failure to provide an adequate dose of medication for adequate periods of time may be the most common cause of "treatment resistance." The second step is to reconsider the diagnosis and/or determine if new diagnoses have emerged since the original consultation. Depression and substance abuse are especially likely to complicate anxiety disorders. Several studies have shown that concomitant personality disorders (axis II) increase the occurrence of resistance to standard treatment and must be addressed through psychotherapy. Last, a variety of possible underlying medical conditions, including thyroid disorder, arrhythmia, and complex partial seizure, should be considered. Then, the clinician should consider a variety of pharmacologic approaches that are specific to each anxiety disorder. Panic disorder patients who are refractory to imipramine frequently respond to high-potency benzodiazepines, monoamine oxidase (MAO) inhibitors, serotonin reuptake inhibitors, or various combinations. Generalized anxiety disorder, if unresponsive to benzodiazepines, may respond to buspirone or a tricyclic antidepressant. Patients with obsessive compulsive disorder who have failed to respond to clomipramine or fluoxetine and other serotonin reuptake blockers may benefit from augmentation strategies using combination therapies including buspirone, fenfluramine, and neuroleptics. Social phobia refractory to beta-blockers and MAO inhibitors may benefit from buspirone, fenfluramine, and neuroleptics. Social phobia refractory to beta-blockers and MAO inhibitors may benefit from buspirone, fluoxetine, or alprazolam.

Brain Stimul. 2008 Apr;1(2):112-21. doi: 10.1016/j.brs.2008.02.001. Epub 2008 Mar 28.
A pilot study of vagus nerve stimulation (VNS) for treatment-resistant anxiety disorders.
George MS1, Ward HE Jr, Ninan PT, Pollack M, Nahas Z, Anderson B, Kose S, Howland RH, Goodman WK, Ballenger JC.
Vagus nerve stimulation (VNS) is an effective anticonvulsant device and has shown antidepressant effects in chronic treatment resistant depression. Because the vagus nerve sends information to brain regions important in anxiety regulation (locus coeruleus, orbitofrontal cortex, insula, hippocampus and amygdala), this pathway might be involved in perceiving or manifesting various somatic and cognitive symptoms that characterize anxiety disorders. On the basis of this reasoning and reports of anxiolytic effects of VNS in patients treated for epilepsy and depression, we organized an open-label pilot acute trial of adjunctive VNS on top of stable medications, followed by long-term follow-up, to assess the safety and potential efficacy of VNS for patients with treatment resistant anxiety disorders.
Eleven adult outpatients with treatment resistant obsessive-compulsive disorder (OCD), panic disorder (PD), or posttraumatic stress disorder (PTSD) were recruited. Patients had failed several medication trials as well as cognitive behavioral therapy (CBT). All patients were rated with the Hamilton Anxiety Scale (HAM-A) and the clinical global impressions improvement scale (CGI-I). Patients with OCD were also rated with the Yale-Brown Obsessive Compulsive Scale (Y-BOCS). Patients were maintained on their current psychotropic medications at fixed doses during the acute 12-week phase. Changes in medications and VNS stimulus parameters were allowed during the long-term follow-up. Response was defined as a 50% or greater improvement on the HAM-A for all patients and a 25% or greater improvement on the Y-BOCS for patients with OCD.
Eleven patients were recruited. Seven patients had a primary diagnosis of OCD, two had PTSD, and one had PD. One OCD patient changed their mind and was never implanted. One patient with OCD withdrew consent before the end of the acute phase, so long-term results were available for nine patients. Three patients were acute responders, based on the HAM-A, and there was some improvement in anxiety ratings over time (with statistically significant improvements at 14 of 18 quarters during long-term follow-up). Of the seven patients with OCD who received stimulation, three were acute responders, based on the Y-BOCS, and there was some improvement in Y-BOCS scores over time (with statistically significant improvements at 7 of 18 quarters during long-term follow-up). VNS was relatively well tolerated. Four years after implantation, four patients (diagnoses two OCD, one PD, one PTSD) were still receiving VNS with continued and sustained improvement in anxiety scores compared with their baseline scores.
These patients with treatment-resistant anxiety disorders generally tolerated VNS treatment, and there was evidence of acute and long-term improvement in some patients. These open data suggest that further double-blind studies assessing the VNS role in treating anxiety disorders, particularly OCD, may be warranted.

Acupunct Med. 2015 Apr;33(2):98-102. doi: 10.1136/acupmed-2014-010524. Epub 2015 Jan 16.
Randomised controlled trial on the use of acupuncture in adults with chronic, non-responding anxiety symptoms.
Errington-Evans N.
A group of adults can be identified with chronic non-responding anxiety symptoms who have repeatedly accessed treatments through their GP, such as cognitive behaviour therapy, bibliotherapy and medication, but with no effect. These patients make heavy use of health service resources with no beneficial outcome. This study aims to test the effect of an acupuncture formula of three specific acupuncture points, suggested in a previous pilot study.
40 participants from a psychiatry waiting list were randomised into one of two groups: group 1 (n=25) received 10 weeks of acupuncture at PC6, HT7 and LR3, and group 2 was a waiting list control group. The waiting list group (n=15) then received acupuncture. Both groups were followed up for 10 weeks after treatment. The outcome measure was the State and Trait Anxiety Inventory.
36 patients completed the study, with two dropouts in each group. State anxiety scores in the acupuncture group decreased from 57.7 (SD 13.1) to 38.8 (12.0); scores in the waiting list control group decreased from 61.5 (11.6) to 60.6 (11.7). The difference was highly significant (p<0.0001). Similar changes were seen for trait anxiety scores. The control group showed similar statistically significant improvements when they received acupuncture. The improvements were maintained after 10 weeks of follow-up in each group.
Acupuncture is a promising intervention for patients with chronic anxiety symptoms that have proven resistant to other forms of treatment.

Treatment-refractory anxiety; definition, risk factors, and treatment challenges
Generalized anxiety disorder with depressive symptoms: could benzodiazepines make anxiety worse? Indicated.
This study is at variance with concerns about noxious effects of benzodiazepines, initially supported by some observational analyses showing that benzodiazepines predicted poor outcome in panic disorder, and were associated with increased anxiety sensitivity, by two small randomized studies suggesting PTSD outcomes might be worse with benzodiazepines, and by a secondary analysis from one benzodiazepine study of GAD showing that outcome was worse compared with imipramine in the subgroup of patients with higher severity depressive symptoms even though they did not meet diagnostic criteria for major depression. However, the addition of a selective benzodiazapine-receptor binding hypnotic agonist, eszopiclone, to an SSRI produced significantly greater improvement in non-sleep-related anxiety symptoms in two separate studies of GAD and PTSD.

^ Lindsay, S.J.E.; Powell, Graham E., eds. (28 July 1998). The Handbook of Clinical Adult Psychology (2nd ed.). Routledge. pp. 152–153. ISBN 978-0-415-07215-1.
Caffiene, alcohol, and benzodiazepine dependence can worsen or cause anxiety and panic attacks.

#5 fishinghat


    Site Partners

  • Active Members
  • PipPipPipPipPipPipPipPipPipPipPipPipPipPipPipPipPipPip
  • 12,311 posts
  • LocationMissouri

Posted 02 July 2017 - 09:09 AM

Treatment Resistant Depression

A total of 59 studies, mostly of low quality, were included in the review, involving multiple treatment comparisons between sertraline and other antidepressant agents. Evidence favouring sertraline over some other antidepressants for the acute phase treatment of major depression was found, either in terms of efficacy (fluoxetine) or acceptability/tolerability (amitriptyline, imipramine, paroxetine and mirtazapine). However, some differences favouring newer antidepressants in terms of efficacy (mirtazapine) and acceptability (bupropion) were also found.

Data from the subset of previously treated depressed patients, who can be considered more difficult to treat, indicate that agomelatine, due to its different mode of action, demonstrated antidepressant efficacy, and favorable side effect profile-with proven benefits in first-line treatment-is also an effective candidate for patients with major depressive disorder previously treated with other antidepressants.

J Affect Disord. 2014 Mar;156:1-7. doi: 10.1016/j.jad.2013.10.043. Epub 2013 Nov 15.
Treatment-resistant depression: definitions, review of the evidence, and algorithmic approach.
McIntyre RS1, Filteau MJ2, Martin L3, Patry S4, Carvalho A5, Cha DS6, Barakat M7, Miguelez M7.
Most adults with major depressive disorder (MDD) fail to achieve remission with index pharmacological treatment. Moreover, at least half will not achieve and sustain remission following multiple pharmacological approaches. Herein, we succinctly review treatment modalities proven effective in treatment-resistant depression (TRD).
We conducted a review of computerized databases (PubMed, Google Scholar) from 1980 to April 2013. Articles selected for review were based on author consensus, adequacy of sample size, the use of a standardized experimental procedure, validated assessment measures and overall manuscript quality.
The evidence base supporting augmentation of conventional antidepressants with atypical antipsychotics (i.e., aripiprazole, quetiapine, and olanzapine) is the most extensive and rigorous of all pharmacological approaches in TRD. Emerging evidence supports the use of some psychostimulants (i.e., lisdexamfetamine) as well as aerobic exercise. In addition, treatments informed by pathogenetic disease models provide preliminary evidence for the efficacy of immune-inflammatory based therapies and metabolic interventions. Manual based psychotherapies remain a treatment option, with the most compelling evidence for cognitive behavioral therapy. Disparate neurostimulation strategies are also available for individuals insufficiently responsive to pharmacotherapy and/or psychosocial interventions.
Compared to non-treatment-resistant depression, TRD has been less studied. Most clinical studies on TRD have focused on pharmacotherapy-resistant depression, with relatively fewer studies evaluating "next choice" treatments in individuals who do not initially respond to psychosocial and/or neurostimulatory treatments.
The pathoetiological heterogeneity of MDD/TRD invites the need for mechanistically dissimilar, and empirically validated, treatment approaches for TRD.

BMC Psychiatry. 2014 Nov 30;14:340. doi: 10.1186/s12888-014-0340-6.
Systematic review of management for treatment-resistant depression in adolescents.
Zhou X, Michael KD, Liu Y, Del Giovane C, Qin B, Cohen D, Gentile S, Xie P.
Current guidelines for treatment-resistant depression in adolescents remain inadequate. This study aimed to systematically review the management of treatment-resistant depression in adolescent patients.
We conducted an electronic database search of PUBMED, EMBASE, Cochrane, Web of Science and PsycINFO for studies with adolescent treatment-resistant depression published up to January 2014. Treatment-resistant depression was defined as failure to respond to at least one course of psychological or pharmacological treatment for depression with an adequate dosage, duration, and appropriate compliance during the current illness episode. The Cochrane risk-of-bias method was used to assess the quality of randomized controlled trials. A meta-analysis of all active treatments was conducted.
Eight studies with 411 depressed adolescents that fit predetermined criteria investigated pharmacological treatments and psychotherapies. Six were open-label studies, and two were randomized controlled trials. The overall response rate for all active treatments investigated was 46% (95% CI 33 to 59; N = 411) with a moderately high degree of heterogeneity (I2 = 76.1%, 95% CI = 47%-86%). When only the two randomized trials were included, the overall response rate of active treatment was 53% (95% CI = 38-67; N = 347). In these randomized trials, SSRI therapy plus CBT was significantly more effective than SSRI therapy alone, while amitriptyline was not more effective than placebo.
Approximately half of the adolescents who presented with treatment-refractory depression responded to active treatment, which suggests that practitioners should remain persistent in managing these challenging cases. The combination of antidepressant medication and psychotherapy should be recommended for adolescents who present with treatment-resistant depression.

J Clin Psychiatry. 2014 May;75(5):477-89; quiz 489. doi: 10.4088/JCP.13r08815.
Repetitive transcranial magnetic stimulation for treatment-resistant depression: a systematic review and meta-analysis.
Gaynes BN1, Lloyd SW, Lux L, Gartlehner G, Hansen RA, Brode S, Jonas DE, Swinson Evans T, Viswanathan M, Lohr KN.
To evaluate the efficacy of repetitive transcranial magnetic stimulation (rTMS) in patients with major depressive disorder (MDD) and 2 or more prior antidepressant treatment failures (often referred to as treatment-resistant depression [TRD]). These patients are less likely to recover with medications alone and often consider nonpharmacologic treatments such as rTMS.
We searched MEDLINE, EMBASE, the Cochrane Library, PsycINFO, and the International Pharmaceutical Abstracts for studies comparing rTMS with a sham-controlled treatment in TRD patients ages 18 years or older.
We included 18 good- or fair-quality TRD studies published from January 1, 1980, through March 20, 2013.
We abstracted relevant data, assessed each study's internal validity, and graded strength of evidence for change in depressive severity, response rates, and remission rates.
rTMS was beneficial compared with sham for all outcomes. rTMS produced a greater decrease in depressive severity (high strength of evidence), averaging a clinically meaningful decrease on the Hamilton Depression Rating Scale (HDRS) of more than 4 points compared with sham (mean decrease = -4.53; 95% CI, -6.11 to -2.96). rTMS resulted in greater response rates (high strength of evidence); those receiving rTMS were more than 3 times as likely to respond as patients receiving sham (relative risk = 3.38; 95% CI, 2.24 to 5.10). Finally, rTMS was more likely to produce remission (moderate strength of evidence); patients receiving rTMS were more than 5 times as likely to achieve remission as those receiving sham (relative risk = 5.07; 95% CI, 2.50 to 10.30). Limited evidence and variable treatment parameters prevented conclusions about which specific treatment options are more effective than others. How long these benefits persist remains unclear.
For MDD patients with 2 or more antidepressant treatment failures, rTMS is a reasonable, effective consideration.

Note - Not a high degree of effectiveness.

Am J Psychiatry. 2013 Oct;170(10):1134-42. doi: 10.1176/appi.ajp.2013.13030392.
Antidepressant efficacy of ketamine in treatment-resistant major depression: a two-site randomized controlled trial.
Murrough JW, Iosifescu DV, Chang LC, Al Jurdi RK, Green CE, Perez AM, Iqbal S, Pillemer S, Foulkes A, Shah A, Charney DS, Mathew SJ.
Ketamine, a glutamate N-methyl-d-aspartate (NMDA) receptor antagonist, has shown rapid antidepressant effects, but small study groups and inadequate control conditions in prior studies have precluded a definitive conclusion. The authors evaluated the rapid antidepressant efficacy of ketamine in a large group of patients with treatment-resistant major depression.
This was a two-site, parallel-arm, randomized controlled trial of a single infusion of ketamine compared to an active placebo control condition, the anesthetic midazolam. Patients with treatment-resistant major depression experiencing a major depressive episode were randomly assigned under double-blind conditions to receive a single intravenous infusion of ketamine or midazolam in a 2:1 ratio (N=73). The primary outcome was change in depression severity 24 hours after drug administration, as assessed by the Montgomery-Åsberg Depression Rating Scale (MADRS).
The ketamine group had greater improvement in the MADRS score than the midazolam group 24 hours after treatment. After adjustment for baseline scores and site, the MADRS score was lower in the ketamine group than in the midazolam group by 7.95 points (95% confidence interval [CI], 3.20 to 12.71). The likelihood of response at 24 hours was greater with ketamine than with midazolam (odds ratio, 2.18; 95% CI, 1.21 to 4.14), with response rates of 64% and 28%, respectively.
Ketamine demonstrated rapid antidepressant effects in an optimized study design, further supporting NMDA receptor modulation as a novel mechanism for accelerated improvement in severe and chronic forms of depression. More information on response durability and safety is required before implementation in clinical practice.

Pharmacological approaches to the challenge of treatment-resistant depression
An excellant review of treatment options for treatment resistant depression.

Beyond Monoamines-Novel Targets for Treatment-Resistant Depression: A Comprehensive Review
An excellant reveiw of unusual approaches and new techniques in treating treatment resistant depression.

J Clin Psychiatry. 2015 Apr;76(4):e487-98. doi: 10.4088/JCP.14r09204.
Comparative efficacy, acceptability, and tolerability of augmentation agents in treatment-resistant depression: systematic review and network meta-analysis.
Zhou X1, Ravindran AV, Qin B, Del Giovane C, Li Q, Bauer M, Liu Y, Fang Y, da Silva T, Zhang Y, Fang L, Wang X, Xie P.
Author information
To comparatively analyze the efficacy, acceptability, and tolerability of various augmentation agents in adult patients with treatment-resistant depression.
An electronic literature search of PubMed, EMBASE, the Cochrane Library, Web of Science, EBSCO, PsycINFO, EAGLE, and NTIS for trials published up to December 2013 was conducted. Several clinical trial registry agencies and US Food and Drug Administration reports were also reviewed. No language, publication date, or publication status restrictions were imposed.
Randomized controlled trials comparing 11 augmentation agents (aripiprazole, bupropion, buspirone, lamotrigine, lithium, methylphenidate, olanzapine, pindolol, quetiapine, risperidone, and thyroid hormone) with each other and with placebo for adult treatment-resistant depression were included.
The proportion of patients who responded to treatment was defined as primary efficacy, and the proportion of all-cause discontinuation and side-effects discontinuation were respectively defined as acceptability and tolerability, which were assessed with odds ratios (ORs) and a Bayesian random-effects model with 95% credible intervals (CrIs).
A total of 48 trials consisting of 6,654 participants were eligible. In terms of the primary efficacy, quetiapine (OR = 1.92; 95% CrI, 1.39-3.13), aripiprazole (OR = 1.85; 95% CrI, 1.27-2.27), thyroid hormone (OR = 1.84; 95% CrI, 1.06-3.56), and lithium (OR = 1.56; 95% CrI, 1.05-2.55) were significantly more effective than placebo. Sensitivity analyses indicated that efficacy estimates for aripiprazole and quetiapine were more robust than those for thyroid hormone and lithium. In terms of acceptability, no significant difference was found between active agents and placebo. In terms of tolerability, compared to placebo, quetiapine (OR = 3.85; 95% CrI, 1.92-8.33), olanzapine (OR = 3.36; 95% CrI, 1.60-8.61), aripiprazole (OR = 2.51; 95% CrI, 1.11-7.69), and lithium (OR = 2.30; 95% CrI, 1.04-6.03) were significantly less well tolerated.
Quetiapine and aripiprazole appear to be the most robust evidence-based options for augmentation therapy in patients with treatment-resistant depression, but clinicians should interpret these findings cautiously in light of the evidence of potential treatment-related side effects.

J Nerv Ment Dis. 2015 Sep;203(9):659-63. doi: 10.1097/NMD.0000000000000348.
Determinants of Treatment-Resistant Depression: The Salience of Benzodiazepines.
Parker GB1, Graham RK.
Treatment-resistant depression (TRD) lacks consensus regarding its definition, despite being common in clinical practice. This study was designed to identify factors contributing to TRD in patients diagnosed with a major depressive disorder. Patients were grouped into "low," "medium," and "high" treatment-resistant (TR) groups based on the number of medications that had been prescribed for their depression. We identified a number of factors linked to TRD. The high TR group was generally older, had a longer depressive episode duration, a higher number of comorbid medical and anxiety disorders, a lower education, and were less likely to be in full-time employment. They also reported less trait irritability and were more likely to view medication as being a contributor to their current depression. Some differences between non-melancholic and melancholic subsets were evident and point to the benefits in research on TRD analyzing the two diagnostic groups separately. The most striking finding was benzodiazepine use, which was significantly more common in the high TR group and within both the melancholic and non-melancholic subsets. Some potential explanations for this finding are offered.

J Clin Psychiatry. 2014 Aug;75(8):e785-93. doi: 10.4088/JCP.13m08725.
Safety, tolerability, and clinical effect of low-dose buprenorphine for treatment-resistant depression in midlife and older adults.
Karp JF1, Butters MA, Begley AE, Miller MD, Lenze EJ, Blumberger DM, Mulsant BH, Reynolds CF 3rd.
To describe the clinical effect and safety of low-dose buprenorphine, a κ-opioid receptor antagonist, for treatment-resistant depression (TRD) in midlife and older adults.
In an 8-week open-label study, buprenorphine was prescribed for 15 adults aged 50 years or older with TRD, diagnosed with the Structured Clinical Interview for DSM-IV, between June 2010 and June 2011. The titrated dose of buprenorphine ranged from 0.2-1.6 mg/d. We assessed clinical change in depression, anxiety, sleep, positive and negative affect, and quality of life. The Montgomery-Asberg Depression Rating scale (MADRS) served as the main outcome measure. Tolerability was assessed by documenting side effects and change in vital signs, weight, and cognitive function. Clinical response durability was assessed 8 weeks after discontinuation of buprenorphine.
The mean dose of buprenorphine was 0.4 mg/d (mean maximum dose = 0.7 mg/d). The mean depression score (MADRS) at baseline was 27.0 (SD = 7.3) and at week 8 was 9.5 (SD = 9.5). A sharp decline in depression severity occurred during the first 3 weeks of exposure (mean change = -15.0 [SD = 7.9]). Depression-specific items measuring pessimism and sadness indicated improvement during exposure, supporting a true antidepressant effect. Treatment-emergent side effects (in particular, nausea and constipation) were not sustained, vital signs and weight remained stable, and executive function and learning improved from pretreatment to posttreatment.
Low-dose buprenorphine may be a novel-mechanism medication that provides a rapid and sustained improvement for older adults with TRD. Placebo-controlled trials of longer duration are required to assess efficacy, safety, and physiologic and psychological effects of extended exposure to this medication.

Am J Psychiatry. 2016 Aug 1;173(8):816-26. doi: 10.1176/appi.ajp.2016.16010037. Epub 2016 Apr 8.
A Double-Blind, Randomized, Placebo-Controlled, Dose-Frequency Study of Intravenous Ketamine in Patients With Treatment-Resistant Depression.
Singh JB1, Fedgchin M1, Daly EJ1, De Boer P1, Cooper K1, Lim P1, Pinter C1, Murrough JW1, Sanacora G1, Shelton RC1, Kurian B1, Winokur A1, Fava M1, Manji H1, Drevets WC1, Van Nueten L1.
Ketamine, an N-methyl-d-aspartate glutamate receptor antagonist, has demonstrated a rapid-onset antidepressant effect in patients with treatment-resistant depression. This study evaluated the efficacy of twice- and thrice-weekly intravenous administration of ketamine in sustaining initial antidepressant effects in patients with treatment-resistant depression.
In a multicenter, double-blind study, adults (ages 18-64 years) with treatment-resistant depression were randomized to receive either intravenous ketamine (0.5 mg/kg of body weight) or intravenous placebo, administered over 40 minutes, either two or three times weekly, for up to 4 weeks. Patients who discontinued double-blind treatment after at least 2 weeks for lack of efficacy could enter an optional 2-week open-label phase to receive ketamine with the same frequency as in the double-blind phase. The primary outcome measure was change from baseline to day 15 in total score on the Montgomery-Åsberg Depression Rating Scale (MADRS).
In total, 67 (45 women) of 68 randomized patients received treatment. In the twice-weekly dosing groups, the mean change in MADRS score at day 15 was -18.4 (SD=12.0) for ketamine and -5.7 (SD=10.2) for placebo; in the thrice-weekly groups, it was -17.7 (SD=7.3) for ketamine and -3.1 (SD=5.7) for placebo. Similar observations were noted for ketamine during the open-label phase (twice-weekly, -12.2 [SD=12.8] on day 4; thrice-weekly, -14.0 [SD=12.5] on day 5). Both regimens were generally well tolerated. Headache, anxiety, dissociation, nausea, and dizziness were the most common (≥20%) treatment-emergent adverse events. Dissociative symptoms occurred transiently and attenuated with repeated dosing.
Twice-weekly and thrice-weekly administration of ketamine at 0.5 mg/kg similarly maintained antidepressant efficacy over 15 days.

Psychother Psychosom. 2014;83(2):70-88. doi: 10.1159/000357500. Epub 2014 Jan 22.
The integrative management of treatment-resistant depression: a comprehensive review and perspectives.
Carvalho AF1, Berk M, Hyphantis TN, McIntyre RS.
Major depressive disorder is a prevalent and disabling illness. Notwithstanding numerous advances in the pharmacological treatment of depression, approximately 70% of patients do not remit after first-line antidepressant treatment.
The MEDLINE/PubMed, EMBASE and ClinicalTrials.gov electronic databases were searched from inception to October 1, 2013, for randomized controlled trials (RCT), relevant open-label trials, meta-analyses and ongoing trials of pharmacological and psychotherapeutic approaches to treatment-resistant depression (TRD).
Switching to a different antidepressant is a useful option following nonresponse to a first-line agent. Although widely used in clinical practice, there is limited evidence to support antidepressant combination for TRD. Notwithstanding evidence for lithium or T3 augmentation to be successful in TRD, most studies were carried out when participants were treated with tricyclic antidepressants (TCA). Of the available strategies to augment the response to new-generation antidepressants, the use of some atypical antipsychotics is best supported by evidence. Several novel therapeutic options are currently discussed. Evidence suggests that cognitive therapy (CT) is an effective strategy for TRD.
The success of switching to a different antidepressant following a first-line agent is supported by evidence, but there is limited evidence for effective combination strategies. Lithium and T3 augmentation of TCA have the strongest evidence base for successful treatment of TRD. The use of augmentation of newer-generation antidepressants with atypical antipsychotics is supported by a growing evidence base. Current evidence supports CT as an effective strategy for TRD. There is a need for additional large-scale RCT of TRD. The development of new antidepressants targeting novel pathways opens a promising perspective for the management of TRD.

Int J Neuropsychopharmacol. 2015 May 25;18(11):pyv060. doi: 10.1093/ijnp/pyv060.
Atypical Antipsychotic Augmentation for Treatment-Resistant Depression: A Systematic Review and Network Meta-Analysis.
Zhou X1, Keitner GI1, Qin B1, Ravindran AV1, Bauer M1, Del Giovane C1, Zhao J1, Liu Y1, Fang Y1, Zhang Y1, Xie P2.
Previous meta-analyses of atypical antipsychotics for depression were limited by few trials with direct comparisons between two treatments. We performed a network meta-analysis, which integrates direct and indirect evidence from randomized controlled trials (RCTs), to investigate the comparative efficacy and tolerability of adjunctive atypical antipsychotics for treatment-resistant depression (TRD).
Systematic searches resulted in 18 RCTs (total n = 4422) of seven different types and different dosages of atypical antipsychotics and a placebo that were included in the review.
All standard-dose atypical antipsychotics were significantly more efficacious than placebo in the efficacy (standardized mean differences [SMDs] ranged from -0.27 to -0.43). There were no significant differences between these drugs. Low-dose atypical antipsychotics were not significantly more efficacious than the placebo. In terms of tolerability, all standard-dose atypical antipsychotics, apart from risperidone, had significantly more side-effect discontinuations than placebo (odds ratios [ORs] ranged from 2.72 to 6.40). In terms of acceptability, only quetiapine (mean 250-350 mg daily) had significantly more all-cause discontinuation than placebo (OR = 1.89). In terms of quality of life/functioning, standard-dose risperidone and standard-dose aripiprazole were more beneficial than placebo (SMD = -0.38; SMD = -0.26, respectively), and standard-dose risperidone was superior to quetiapine (mean 250-350 mg daily).
All standard-dose atypical antipsychotics for the adjunctive treatment of TRD are efficacious in reducing depressive symptoms. Risperidone and aripiprazole also showed benefits in improving the quality of life of patients. Atypical antipsychotics should be prescribed with caution due to abundant evidence of side effects.

J Clin Psychiatry. 2015 Sep;76(9):e1147. doi: 10.4088/JCP.14052wc1c.
Using mechanism of action to choose medications for treatment-resistant depression.
Thase ME1, Schwartz TL.
Remission rates for depression continue to be low, and for many patients, complex treatment regimens are needed for optimal response. Many physicians do not fully understand how and why depression medications work or which ones will complement each other. This CME Webcast covers the different mechanisms of action of current pharmacotherapeutic options for depression, both monotherapy and adjunctive medications, and shows clinicians how to use their understanding of mechanisms of action to choose the most effective treatment strategy for their patients, especially those with treatment-resistant or difficult-to-treat depression.

Eur Neuropsychopharmacol. 2015 Apr;25(4):441-53. doi: 10.1016/j.euroneuro.2015.01.001. Epub 2015 Feb 2.
The combined effect of genetic polymorphisms and clinical parameters on treatment outcome in treatment-resistant depression.
Kautzky A1, Baldinger P1, Souery D2, Montgomery S3, Mendlewicz J4, Zohar J5, Serretti A6, Lanzenberger R1, Kasper S7.
For over a decade, the European Group for the Study of Resistant Depression (GSRD) has examined single nucleotide polymorphisms (SNP) and clinical parameters in regard to treatment outcome. However, an interaction based model combining these factors has not been established yet. Regarding the low effect of individual SNPs, a model investigating the interactive role of SNPs and clinical variables in treatment-resistant depression (TRD) seems auspicious. Thus 225 patients featured in previous work of the GSRD were enrolled in this investigation. According to data availability and previous positive results, 12 SNPs in HTR2A, COMT, ST8SIA2, PPP3CC and BDNF as well as 8 clinical variables featured in other GSRD studies were chosen for this investigation. Random forests algorithm were used for variable shrinkage and k-means clustering for surfacing variable characteristics determining treatment outcome. Using these machine learning and clustering algorithms, we detected a set of 3 SNPs and a clinical variable that was significantly associated with treatment response. About 62% of patients exhibiting the allelic combination of GG-GG-TT for rs6265, rs7430 and rs6313 of the BDNF, PPP3CC and HTR2A genes, respectively, and without melancholia showed a HAM-D decline under 17 compared to about 34% of the whole study sample. Our random forests prediction model for treatment outcome showed that combining clinical and genetic variables gradually increased the prediction performance recognizing correctly 25% of responders using all 4 factors. Thus, we could confirm our previous findings and furthermore show the strength of an interaction-based model combining statistical algorithms in identifying and operating treatment predictors.

Note - Shows a strong connection between genetic mutations and treatment resistant depression. Genetic testing was able to help develop an individual treatment protocol.

Int J Psychiatry Clin Pract. 2013 Oct;17(4):313-6. doi: 10.3109/13651501.2013.798418. Epub 2013 May 20.
Possible usefulness of tianeptine in treatment-resistant depression.
Tobe EH1, Rybakowski JK.
Tianeptine is an atypical antidepressant drug, augmenting serotonin reuptake and preventing stress-associated changes in the brain. In this paper, we present the use of tianeptine in eight American treatment-resistant patients with major depressive disorder.
Two male and six female patients with major depressive disorder, aged 44-72 years with duration of the illness 3-40 years, were studied. All met criteria for treatment-resistant depression (TRD) as they failed four or more trials of medication, and two failed both ECT and Vagal Nerve Stimulation trials. In three patients, the drug was used as monotherapy, and in five, it was added to ongoing antidepressant treatment.
The remission (≤ 7 points on the 17-item Hamilton Depression Rating Scale) after 8 weeks of treatment was obtained in four female patients (50%). Of them, three still require other psychotropic medications to remain in remission and all four responders have been in remission with ongoing treatment with tianeptine for > 2 years. In two patients, the drug was terminated due to the incidence of delirium, and in one, it was due to severe agitation.
The results may suggest a possible usefulness of tianeptine in selected patients with TRD. They also point to a possible serious side effect of this drug not hitherto reported.

The Potential Utility of Pharmacogenetic Testing in Psychiatry
Kathryn R. Gardner, Francis X. Brennan, Rachel Scott, and Jay Lombard
Over the last decade, pharmacogenetics has become increasingly significant to clinical practice. Psychiatric patients, in particular, may benefit from pharmacogenetic testing as many of the psychotropic medications prescribed in practice lead to varied response rates and a wide range of side effects. The use of pharmacogenetic testing can help tailor psychotropic treatment and inform personalized treatment plans with the highest likelihood of success. Recently, many studies have been published demonstrating improved patient outcomes and decreased healthcare costs for psychiatric patients who utilize genetic testing. This review will describe evidence supporting the clinical utility of genetic testing in psychiatry, present several case studies to demonstrate use in everyday practice, and explore current patient and clinician opinions of genetic testing.

A few of the companies that offer genetic testing. It is a simple mouth swab sent off to their lab for genetic testing.

• Wrong diagnosis (10% to 15% of treatment resistant depression is actually something other than depression) (such as, thyroid disease, nutritional deficiencies, sleep apnea, “latent” bipolarity)


0 user(s) are reading this topic

0 members, 0 guests, 0 anonymous users