Tag Archives: monoamine oxidase inhibitors

Prozac : 50% Placebo Effect?

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.



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

What Kind of Therapy is Out There?

In reviewing treatments for depression, it seems the three most common, two of which are very broad, treatments are anti depressant medications, electro-convulsive therapy or ECT, and psychotherapy. Each of these treatments has their own purpose and regimen and can be combined in various ways even though they are different. In fact it is most likely because they are so different that they work well together.

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Antidepressant medication gives a therapist and a patient many options. These options have both positive and negative effects. There are different side effects with each type of medication, some tolerable, some need to be managed with other medications. It is different for everyone; this is why it is important to continue trying different combinations until an agreeable treatment plan is found. One example of medication is SSRIS, which are Selective Serotonin Reuptake Inhibitors. This medication is usually the first choice for treatment. The reasoning behind this is that SSRI’s are the most tolerated with very little side effects and most people find they work very well for them. Some side effects are headache or insomnia, but often any side effects subside in the first month. This medication allows a high amount of serotonin to be blocked in the synapse. By doing this, the cells that are neglected are resaturated allowing relief from depression symptoms.

Tricyclic anti-depressants or TCAs are a second choice in medications, if for some reason the SSRI is unable to help the patient. This medication was developed sometime during the 1950’s and 60’s. TCAs seem to be used for more moderate or severe depression because the side effects are more likely to be serious. TCAs work in the brain synapses and increase norepinephrine. Some of the side effects include dry mouth or visual focus, but the more serious side effects include things such as urinary obstruction or delirium. People who have had a lot of strokes or have been diagnosed as having seizure disorders should not be given any TCAs as medication.

MAOIs or monoamine oxidase inhibitors are another common medication prescribed to depression patients. These are generally a last choice because the side effects are often serious. MAOIs are usually effective in treating depression and were actually the first anti-depressant. It works by blocking monoamine oxidase in the brain synapses and increasing norepinephrine. MAOIs inhibit the body’s ability to break down tyramine which is found in very common foods such as wine, nuts, and chocolate. When this food is consumed while the person is taking an MAOI, it is possible for the tyramine to cause blood pressure to rise to dangerous levels.

While anti-depressants can be mixed or left as a single treatment, they do provide a lot of options to help deal with side effects or other issues that may come up.  They are always the best option; another treatment option for depression is electroconvulsive therapy or ECT.

When electroconvulsive therapy is chosen as treatment the patient receives an electrical current which is passed through the brain causing a seizure. The seizure usually continues for twenty to ninety seconds. This treatment is said to offer a patient a quick relief of their depression symptoms. A common side effect of this treatment is confusion that can last up to several hours and short term memory loss, both of which are short term.

Psychotherapy is the last type of treatment discussed and is often referred to as talk therapy. There are various types of psychotherapy such as cognitive behavioral therapy, interpersonal therapy, and psychodynamic therapy. The most common type of talk therapy is the cognitive behavioral therapy. During sessions a patient not only talks about their depression, they have the opportunity to learn more about it. The patient is then able to focus on knowing what their negative patterns are and changing those into positive behaviors. Interpersonal therapists’ help their patients look at the destructive relationships a person is in that may be helping to grow the depression instead of helping to keep it at bay. Psychodynamic therapy helps a patient work through and resolves whatever internal conflicts the patient may be living with.

All of these types of psychotherapy focus on one thing, helping the patient talk through and learn how to deal with events in their lives so they don’t feel like they are drowning in depression.

Out of all of these treatments I would actually think electroconvulsive therapy to be the quickest and most effective. I can’t imagine going under sedation in order to endure treatment and then waking up not only with memory loss but also being confused about your whereabouts, among other things, even if only temporarily.

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Child and Adolescent Psychological Disorders.

Oxford Textbook of Psychopathology.

Depression. medicinenet.com. http://www.medicinenet.com/script/main/art.asp?articlekey=342&pf=3&page=6

Depression (Major Depression).  Mayoclinic.com. http://www.mayoclinic.com/health/depression/DS00175/METHOD=print&DSECTION=all