All you need to know about Prozac

Severe abstinence symptoms could happen in patients who suddenly discontinued Prozac therapy. It is supposed that adverse effects of the Prozac discontinuation are mild enough. There are two recommended strategies to manage with discontinuation syndrome:

1. To reduce gradually dose of Prozac;
2. To replace Prozac with the other SSRI agent, in situations when gradual changes off the Prozac dose is ineffective.

It was proved in some double-blind controlled studies.

There were some blind trials where discontinue of antidepressant therapy for a short time (4–8 days) with further renewal has been studied. It was found out that the most severe side effects had been caused with interruption of paroxetine. Interruption of Zoloft therapy induced severe adverse effects but milder then paroxetine. Prozac showed the best tolerance in that study. Slow elimination of Prozac from the body can explain that result.

32% of members of Prozac discontinued group complain about new or worsened side effects versus 27%of patients who continued treatment in a longer, 6 week-long, blind discontinuation study. Significantly higher 5-7% rate of dizziness at weeks 4-6 and 4% rate of somnolence at week 2 were reported by the patients who had interrupted therapy. Long Prozac half-life in the body was proved with withdrawal symptoms, lasting for a long time. People reported about dizziness persisting to the end of the study

Concentration of Prozac can achieve relatively high levels. It becomes maximal in 6-8 hours after medicine intake. Plasma proteins, particularly albumin, highly bind Prozac.
Enzyme CYP2D6 of cytochrome P450 system helps to metabolize Prozac. Reaction of Prozac metabolism happens in the liver. There is wide range of genetic variability in the function of CYP2D6 that’s why the role of that enzyme in the metabolism of Prozac may be clinically essential.
The distinctive feature of Prozac and its active metabolite norfluoxetine from other antidepressant medications is their very slow excretion. Half –life of Prozac elimination can vary from 1-3 days after single dose to 4-6 day of after continuous use. Likewise, the half-life of norfluoxetine becomes longer (16 days) after long termed use. That fact can be explained due to that Prozac and norfluoxetine inhibit their own metabolism with time. That’s why drug and its active metabolite concentration in blood keeps on growing during the first weeks of therapy, and their steady concentration in the blood is achieved only after four weeks after treatment beginning. Moreover, the brain levels of Prozac and its metabolites have been increasing through at least the first five weeks of treatment. A patient receives the full benefits of the current dose for at least a month since its initiation. The average of achieving consistent response is about 29 days. Likewise, complete elimination of Prozac may take several weeks. The brain levels of Prozac run down only by 50% during the first week after the treatment had been discontinued, The blood level of norfluoxetine after 4 weeks the treatment discontinuation is about 80% of the level registered by the end of the first treatment week, and after 7 weeks the treatment had been discontinued it is still possible to detect norfluoxetine in the blood.
Prozac levels in brain increases very slowly during first 5 weeks of therapy. It is distinction feature of Prozac’s pharmacokinetics. That fact aggravates to find out the most optimal dose for continuous treatment. It was proved that one 60-mg dose of Prozac per week has similar effect as 20 mg/day for the continuation treatment of patients responding to 20 mg/day of Prozac. 5 mg/day Prozac was significantly superior to placebo and equivalent to 20 mg/day; while Prozac 80 mg/week had similar results as 60 mg/day Prozac or 150 mg/day amitriptyline. Increasing of dose to 60mg/day in patients who did not respond to 20mg/day therapy is not essentially different from results got in patients continuing the 20 mg/day treatment.
There is speculation based on the results of recent trials. It tries to explain the resistance to the SSRIs Paxil and Celexa. That hypothesis says that the genetic variation of P-glycoprotein (Pgp) transporter can induce resistance to abovementioned medications. Paxil and Celexa are Pgp substrates and Pgp carries them from the brain, while Prozac is not a substrate of that protein. That’s why replacement of Paxil and Celexa with Prozac can bring positive dynamics in patients who don’t respond on those drugs.

Cooperation between Bryan Molloy and Robert Rathbun in 1970 at leaded to utility invention of Prozac.

Antihistamine diphenhydramine showed some antidepressant-like properties. That fact was known at that time. These scientists chose 3-phenoxy-3-phenylpropylamine (a compound structurally similar to diphenhydramine) as terminus a quo. Dozens of its derivatives have been synthesized by Molloy. A selective norepinephrine reuptake inhibitor Nisoxetine became a result of proving the physiological effects of those agents in mice.

Another Eli Lilly scientist, David Wong, trying to discover a derivative inhibiting only serotonin reuptake, suggested that series of laboratory researches dedicated to reuptake of serotonin, norepinephrine and dopamine should be prospected again. In May 1972 Jong-Sir Horng carrying out that test discovered agent which was named later Prozac. It acted as the most potent and effective selective inhibitor of serotonin reuptake of the series.

Lilly scientists claimed Prozac to be the first selective serotonin reuptake inhibitor (SSRI). But they had to issue a correction two years later,where they declared that zimelidine developed by Arvid Carlsson and colleagues had been the first SSRI.

In August 2001 Prozac patent of Eli Lilly expired that induced inflow of generic drugs onto the market. Eli Lilly rebranded Prozac as “Sarafem” for the treatment of premenstrual dysphoric disorder in attempt to reimburse loss caused with reduction of sales of Prozac in Eli Lilly.

FDA has approved Prozac as the treatment of major depression (MDD), obsessive compulsive disorder (OCD), bulimia nervosa and panic disorder. Prozac proved its efficacy for depression in 6-week long double-blind controlled trials where it also relieved anxiety and improved sleep. Prozac was more effective against placebo for the prevention of depression relapse when the patients, who originally responded to Prozac, were treated for a further 38 weeks. It was found out in placebo-controlled trials that Prozac therapy is effective both in geriatric and pediatric depression.

Physicians can prescribe Prozac for treatment OCD both in adults and children. As against to depression treatment higher doses of Prozac have been more effective in treatment of Obsessive–compulsive disorder. Prozac approved itself as perfect drug in treatment of patients suffering from panic disorder. Using Prozac therapy in such patients leads to exceeding reduction of frequency of panic attacks. Quantity of binge-eating and purging episodes of bulimia nervosa can be significantly decreased if Prosac is taken. It was proved that using placebo for the prevention of bulimia nervosa is not nearly as good as long-termed (year-long) Prozac treatment.