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Antidepressants and other psychotropic medications

Related articles: Anxiety, Depression

Anxiety and depression are frequent symptom complaints among the chronically ill. They are also among the symptoms that can be exacerbated by excess exposure to light.

Patients considering the Marshall Protocol (MP) may already be taking anti-anxiety agents and antidepressants. As with many drugs, these can act in immunomodulatory ways, sometimes in ways that have yet to be fully understood.

Although the ultimate goal is to discontinue taking these medications, patients experiencing intolerable anxiety or depression should seek relief. If anti-anxiety agents and antidepressants palliate severe symptoms and allow patients to continue the MP in a safe and tolerable manner, these drugs are not contraindicated.

It is important to point out that many patients report that depression and anxiety resolve over the course of treatment with the MP.

Types of anti-anxiety agents and antidepressants

The following is a list of some common anti-anxiety agents and antidepressants.

  • amitriptyline (Apo-amitriptyline, Elatrol, Elavil, Endep, Laroxyl, Saroten, Sarotex, Tryptizol)
  • aripiprazole (Abilify), bupropion (Budeprion SR/XL, Bupropion SR/XL, Wellbutrin SR/XL, Zetron, Zyban SR)
  • citalopram (Alcytan, Celexa, Cipramil, Cittá)
  • diazepam (Ducene, Ivax Pharm, Stesolid, Valium)
  • duloxetine (Cymbalta)
  • escitalopram (Cipralex, Esipram, Lexapro, Seroplex)
  • fluoxetine (Actan, Fluxene, Lorien, Lovan, Prozac, Tuneluz)
  • fluphenazine (Modecate, Prolixin Decanoate, Dapotum D, Anatensol, Fludecate, Sinqualone Deconoate, Dapotum Injektion, Flunanthate, Moditen Enanthate Injection, Sinqualone Enanthate, Prolixin, Permitil, Dapotum, Lyogen, Moditen, Omca, Sediten, Selecten, Sevinol, Sinqualone, Trancin) – shown to be “a direct inhibitor of the innate immune signaling pathway”1
  • nortriptyline (Aventyl, Norpress, Pamelor)
  • paroxetine (Aropax, Paxil, Paxil CR, Paxxet, Pexeva, Sereupin, Seroxat)
  • S-Adenosyl-L-Methionine (SAM-e)
  • sertraline (Eleva, Lustral, Sertra, Xydep, Zoloft) – shown to be “a direct inhibitor of the innate immune signaling pathway”2
  • St. John's wort – contains about a dozen compounds of potential pharmacological activity. St. John's wort induces hepatic drug metabolism through activation of the pregnane X receptor, among other mechanisms. The activation of PXR would give immunosupression similar to minocycline. Contraindicated.
  • trazodone (APO-Trazodone, Desyrel, Donaren)
  • trifluoperazine (Eskazinyl, Eskazine, Jatroneural, Modalina, Stelazine, Terfluzine, Trifluoperaz, Triftazin) – shown to be “a direct inhibitor of the innate immune signaling pathway”3
  • venlafaxine (Effexor, Effexor XR, PMS-Venlafaxine XR, Venlafaxine XR)

According to Trevor Marshall, PhD:

Brand name Valium product does not seem to be addictive in our cohort, whereas there are problems weaning off some of the generics.

Lithium

According to published reports, lithium affects the immune system profoundly.

Lithium has some antiviral effects. A 2000 study stated that the drug has been shown to have antiviral effects in experimental and clinical conditions, particularly against herpes viruses.4 However, the antidepressant's immunosuppressive effects may be dominant over its anti-infective impact. Lithium may exacerbate autoimmune conditions such as thyroiditis or rarely Graves' disease.5 The common clinical side effects of the drug are goitre (swelling in the thyroid gland) in up to 40% and hypothyroidism in about 20%.

Patients or physicians contemplating the Marshall Protocol should work out a plan with their doctor to wean lithium prior to beginning minocycline.

Efficacy

As described in a Medscape article, a 2010 review of four meta-analyses of efficacy trials submitted to the US Food and Drug Administration (FDA) suggests that antidepressants are only “marginally efficacious” compared with placebo and “document profound publication bias that inflates their apparent efficacy.”6

In addition, when the researchers also analyzed the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial, “the largest antidepressant effectiveness trial ever conducted,” they found that “the effectiveness of antidepressant therapies was probably even lower than the modest one reported…with an apparent progressively increasing dropout rate across each study phase.

“We found that out of the 4041 patients initially started on the SSRI [selective serotonin reuptake inhibitor] citalopram in the STAR*D study, and after 4 trials, only 108 patients had a remission and did not either have a relapse and/or dropped out by the end of 12 months of continuing care,” lead study author Ed Pigott, PhD, a psychologist with NeuroAdvantage LLC in Clarksville, Maryland, told Medscape Medical News.

“In other words, if you're trying to look at sustained benefit, you're only looking at 2.7%, which is a pretty jaw-dropping number,” added Dr. Pigott.

Overall, “the reviewed findings argue for a reappraisal of the current recommended standard of care of depression,” write the study authors.

Adverse effects

  • atherosclerosis – Antidepressants may boost mood at the expense of accelerated atherosclerosis for middle-age men, according to an observational study of more than 500 twins who had served in the Vietnam War.7
  • obesity – According to a 2009 JAMA article, subjects treated with antipsychotics became overweight or obese in as little as 12 weeks.8 A team led by Dr. Christoph Correll of Zucker Hillside Hospital and the Feinstein Institute for Medical Research in New York studied 272 children and teens aged 4 to 19 with bipolar disorder, schizophrenia and disruptive or aggressive behavior spectrum disorders.9 After roughly 11 weeks, those who took Zyprexa gained an average of 18.7 pounds (8.5 kg), those on Seroquel gained 13.4 pounds (6.1 kg), those on Risperdal gained 11.7 pounds (3.5 kg) and those on Abilify gained 9.7 pounds (4.4 kg). “The weight gain is dramatic, rapid and pervasive,” Correll said in a telephone interview.
  • risk of autism – A case control study, which looked at medical records of California mothers, found that expectant mothers who took an antidepressant medication increased their risk of delivering a child with autism spectrum disorder (ASD).10 The 2011 analysis suggested that exposure to a selective serotonin reuptake inhibitor, particularly during the first trimester, may somewhat increase the risk of ASD.

Weaning off anti-anxiety agents and antidepressants

MP patients should consult with their physicians as their symptoms resolve to experiment with taking lower levels of anti-anxiety agents and antidepressants. Weaning anti-anxiety agents and antidepressants may increase immunopathology.

Though patients on anti-depressants tend to have more extreme Herx [immunopathology] reactions, and there is evidence suggesting antibiotic effects of psychiatric meds which may be counter-productive to the intention of the MP, I do not recommend reduction of anti-depressants until symptoms improve.

Then, very gradual reduction of anti-depressants can be initiated, but one should expect that it will take months and months to slowly wean off.

Greg Blaney, MD

Read more

  • The Epidemic of Mental Illness: Why? – In an essay in The New York Review of Books, Marcia Angell, former editor in chief of The New England Journal of Medicine, favorably entertains the premise that “psychoactive drugs are useless.”
  • Fluoxetine inhibits coxsackie virus replication – A 2012 study showed that Prozac reduced the synthesis of viral RNA and protein.11

Notes and comments

Canadian judge rules SSRI antidepressants like Prozac can cause children to commit murder … http://www.naturalnews.com/034433_SSRI_drugs_children_murder.html

Broad Review of FDA Trials Suggests Antidepressants Only Marginally Better than Placebo

http://www.medscape.com/viewarticle/727323

My doc told me…'it's all a crap shoot anyway with psych drugs.'

'Just when you think you have somebody balanced out just right….they explode all over again'

He's pretty realistic…..so he doesn't mind prescribing the MP.

seanlane

Not sure if the Correll study is accurate

From: Dr Trevor MarshallDate: 2011-02-09 20:37:05 Reply: http://www.marshallprotocol.com/reply.php?topic_id=14045

Even a short time on antipsychotics may increase the risk of heart disease:

http://www.reuters.com/article/2011/02/09/us-antipsychotics-heart-idUSTRE71871020110209

http://archpsyc.ama-assn.org/cgi/content/abstract/archgenpsychiatry.2011.2v1 Foley and her team looked at 25 previous studies that had tracked risk factors for heart disease in patients taking older or newer antipsychotics. These included high blood pressure, cholesterol levels, and body weight. They found that across all the studies, six to seven of every 10 people on antipsychotics were overweight after six months. Before taking the drugs, only about four of every 10 were overweight, the same as in the general population.

Commonly Used Antidepressants May Also Affect Human Immune System ScienceDaily (Jan. 20, 2006) — Drugs that treat depression by manipulating the neurotransmitter serotonin in the brain may also affect the user's immune system in ways that are not yet understood, say scientists from Georgetown University Medical Center and a Canadian research institute.

That's because the investigators found, for the first time, that serotonin is passed between key cells in the immune system, and that the chemical is specifically used to activate an immune response. They do not know yet, however, whether these SSRI (selective serotonin reuptake inhibitors) drugs “including the brands Prozac, Zoloft, Paxil and others” could have either a beneficial or a damaging effect on human immunity. “The wider health implication is that commonly used SSRI antidepressants, which target the uptake of serotonin into neurons, may also impact the uptake in immune cells,” said Gerard Ahern, Ph.D., assistant professor of Pharmacology at Georgetown and lead researcher on the study. He said that while it may be possible that SSRI drugs may restore a healthy immune function in people who are depressed and prone to infections, it is possible that they might also bolster immunity to the point that they trigger autoimmune disease. “At this point we just don't know how these drugs might affect immunity, so we really need to clarify the normal role of serotonin in immune cell functioning,” Ahern said. The surprising finding that serotonin is rapidly passed between immune cells in a manner similar to its transmission between brain neurons was revealed in mid-October, when the research team published the findings in the journal Blood. In December, the discovery was highlighted for the general scientific audience by the journal Nature Reviews Immunology, and now the research team is working to produce an animal model that may help describe the precise nature of this interaction. “The novelty is that we reveal a potential communication, involving the transmitter serotonin, between immune cells that is normally only found between neurons,” Ahern said. In addition to Ahern, Peta Connell, Ph.D., from the Robarts Research Institute in Canada, was also a co-lead researcher on the study. Scientists from the Robarts Research Institute also contributed to the work. In the brain, serotonin transmission between neurons is associated with feelings of pleasure, mood, and appetite, and the class of antidepressants known as SSRIs keeps serotonin active within the synaptic spaces between neurons, enhancing the chemical's positive effects. Unlike in the brain, which uses chemical messengers to communicate between nerve cells, the immune system is believed to “converse” through physical contact – one type of immune cell touches another, setting off a response. Specifically, “antigen presenting cells” display their antigens (bits of a foreign invader) to T-cells, and a resulting physical coupling between the antigens and the T-cells will prompt the T-cells to divide and expand in population, triggering an immune response designed to destroy the invader. This process may take hours. What the Georgetown researchers found, however, is that dendritic cells – the most powerful of the antigen-presenting cells and the ones that can find invaders that have never infected the body and “educate” the immune system to fight them – also use serotonin to quickly excite a T-cell response. They discovered that these dendritic cells can rapidly secrete serotonin, which activates serotonin receptors on certain types of T-cells. “In addition to the physical contact, it surprised us to find that these immune cells also have machinery to take up serotonin and to secrete it in an excitatory manner,” Ahern said. “The point behind this transmission is not entirely clear, but it appears to be an additional way of stimulating a T cell response.” Drugs that block serotonin reuptake “likely change some of the parameters of T-cell activation, but we don't know yet if it enhances or inhibits the total immune response,” Ahern said. “But it is something that should be explored because we really have no idea what SSRIs are doing to people's immune systems.”

References

1 , 2 , 3 Zhu J, Smith K, Hsieh PN, Mburu YK, Chattopadhyay S, Sen GC, Sarkar SN High-throughput screening for TLR3-IFN regulatory factor 3 signaling pathway modulators identifies several antipsychotic drugs as TLR inhibitors. J Immunol. 2010;184:5768-76.
4 Rybakowski JK Antiviral and immunomodulatory effect of lithium. Pharmacopsychiatry. 2000;33:159-64.
5 Lazarus JH Lithium and thyroid. Best Pract Res Clin Endocrinol Metab. 2009;23:723-33.
6 Pigott HE, Leventhal AM, Alter GS, Boren JJ Efficacy and effectiveness of antidepressants: current status of research. Psychother Psychosom. 2010;79:267-79.
7 Shah AJ, et al “Association of antidepressant medications with carotid intima media thickness in middle aged veteran twins” ACC 2011.
8 Correll CU, Manu P, Olshanskiy V, Napolitano B, Kane JM, Malhotra AK Cardiometabolic risk of second-generation antipsychotic medications during first-time use in children and adolescents. JAMA. 2009;302:1765-73.
9 Maayan L, Correll CU Management of antipsychotic-related weight gain. Expert Rev Neurother. 2010;10:1175-200.
10 Croen LA, Grether JK, Yoshida CK, Odouli R, Hendrick V Antidepressant Use During Pregnancy and Childhood Autism Spectrum Disorders. Arch Gen Psychiatry. 2011;:.
11 Zuo J, Quinn KK, Kye S, Cooper P, Damoiseaux R, Krogstad P Fluoxetine is a potent inhibitor of coxsackievirus replication. Antimicrob Agents Chemother. 2012;56:4838-44.
Last modified: 08.28.2012
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