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Prozac : 50% Placebo Effect?

Posted Aug 07 2012 12:00am

It goes by names – Fluoxetine, Rapiflux, Sarafem, Selfemra, Oxactin, Ranflutin – but it is best known as Prozac.  Prozac is a Selective Serotonin Reuptake Inhibitor (SSRI).  SSRI’s are a class of drugs intended to block reuptake of serotonin, a mood regulating neurotransmitter, at the synapse.  The inhibition of the reuptake process is believed to cause an increase in the concentration of the neurotransmitter, in this case Serotonin, at the synapse.  (Kelsey, Newport, & Nemeroff, 2006, p. 28)  Other examples of this class of drugs include Citalopram (Celexa), Escitalopram (Lexapro), Fluvoxamine (Luvox), Paroxamine (Paxil), and Sertaline (Zoloft). (Kelsey et al., 2006, p. 47)

The history of SSRIs is one laden with concerns about side effects of their antidepressant predecessor,  Tricyclic Antidepressants (TCAs), and before them, Monoamine Oxidase Inhibitors (MAOIs).  Both classes of drugs are laden with side effects because they possess “rich pharmacology” as compared to the more targeted and selective SSRIs.  “In 1983, the first SSRI, fluvoxamine (Luvox), debuted in Switzerland.  Five years later, Fluoxetine (Prozac) was introduced in the United States.  The SSRIs revolutionized the treatment of depression.”  (Kelsey et al., 2006, p. 54)  SSRIs improved safety and tolerability – removing much of the stigma of taking an antidepressant.

SSRI’s are not without side effects, particularly because serotonin is so widely distributed in the brain.  Despite the fact that SSRIs have an overall effect of increasing and stabilizing mood for most people, they may also produce abdominal discomfort, sexual dysfunction, and anxiety.  (Kelsey et al., 2006, p. 54)  The response one can expect from an SSRI is highly individualized – every patient or client responds differently.  When starting an SSRI it is important to titrate (or gradually increase) dosages to avoid abrupt increases in serotonin.  Abrupt increases have led to headache, sleep issues, anxiety, and a host of other (mostly tolerable and short-term, comparatively speaking) side effects.  Longer term side effects include delayed orgasm, impotence, and decreased desire to have sexual relations.  It bears mentioning this can be a nice perk for men who are prone to premature ejaculation.  Abruptly stopping SSRIs can produce a constellation of symptoms affectionately called “serotonin discontinuation syndrome.”  (SDS) (Kelsey et al., 2006, p. 55)  Nausea, abdominal pain, irratibility, anxiety, and “shock-like sensations are among the most common signs and symptoms of SDS.  Aside from depression, the disorder for which SSRIs are primary intended, some SSRIs have proven to be effective in the treatment of Dysthymic Disorder, the depressive phase of Bipolar Disorder, Premenstrual Dysphoric Disorder, Panic Disorder, Social Phobia, OCD, Bulimia Nervosa, and Binge-Eating Disorder.  (Kelsey et al., 2006, p. 55)

Prozac holds a number of unique qualities within the more general category of SSRIs.  Aside from being the most prescribed antidepressant in the world for many years, it is notable for its long half life.  This longer action causes the “washout time” to take longer, but is undoubtedly a positive for clients who periodically miss a dose due to poor compliance.  There is also a once-a-week depot type dose for those individuals that do not wish to take pills daily.  Dosages range from 20mg-80mg once daily, usually in the morning.  (Kelsey et al., 2006, p. 55)

The prognosis or expected outcome from this drug is hard to predict because every individual patient responds differently to it.  Common side effects are addressed above, but if side effects are intolerable, or the positive effects are not clinically significant – the most likely scenario is “try a different one.”  Long story short – antidepressants are a crap shoot.  The patient should expect to get a markedly uptake in mood after taking Prozac for 4 weeks.  Discontinuation symptoms are rare when compared with other SSRIs.  Half of people who take Prozac may be just as well off with a sugar pill due to the placebo effect, with as little as 25% of Prozac users actually responding to the drug itself.  (Kirsch & Sapirstein, 1998)  Some believe that the field has inappropriately ignored the overshadowing role of the placebo effect and have rushed to declare victory for SSRIs, but not everyone is so hip on that hypothesis.  (Beutler, 1998)  There is no shortage of controversy around this particular article, however, including concerns about the absence of no-treatment effect sizes and other questionable statistical methodology.  (Dawes, 1998)  It should also be noted that the data is almost 15 years old.  More recent research failed to support the hypothesis that avoidance enhancement would be enhanced by Prozac (in goldfish).  The implications on the treatment of other vertebrates remains to be seen since it is hypothesized that serotonin mechanism may be higher conserved in vertebrate evolution.  (Beulig & Fowler, 2008)  The bottom line – your mileage may vary – consult with a psychiatrist.

 

References

Beulig, A., & Fowler, J. (2008). Fish on prozac: Effect of serotonin reuptake inhibitors on cognition in goldfish. Behavioral Neuroscience, 122(2), 426-432. doi: 10.1037/0735-7044.122.2.426

Beutler, L. E. (1998). Prozac and placebo: There’s a pony in there somewhere. Prevention & Treatment, 1(2). doi: 10.1037/1522-3736.1.2.13c

Dawes, R. M. (1998). Listening to prozac but hearing placebo: Commentary on kirsch and saperstein. Prevention & Treatment, 1(2). doi: 10.1037/1522-3736.1.1.15c

Kelsey, J. E., Newport, D. J., & Nemeroff, C. B. (2006). Principles of psychopharmacology for mental health professionals. Hoboken, NJ: John Wiley & Sons.

Kirsch, I., & Sapirstein, G. (1998, Jun). Listening to Prozac but hearing placebo: A meta-analysis of antidepressant medication. Prevention & Treatment, 1(2). doi: 10.1037/1522-3736.1.1.12a

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