Monoamine oxidase inhibitors fluoxetine

Monoamine Oxidase Inhibitors (MAOIs). Controlled trials comparing the M AOl phenelzine to clomipramine or fluoxetine have produced mixed results. Given the limited data regarding any efficacy of MAOIs in the treatment of OCD coupled with their potentially dangerous interactions, we cannot recommend MAOIs in the treatment of OCD until other approaches have been tried. 

Switching patients to or from a monoamine oxidase inhibitor (MAOl) Allow at least 14 days to elapse between discontinuation of a MAOl and initiation of SSRI therapy. Similarly, allow at least 14 days (at least 5 weeks for fluoxetine) after stopping an SSRI before starting an MAOl. 

Hypersensitivity to SSRIs in combination with a monoamine oxidase inhibitor (MAOl), or within 14 days of discontinuing an MAOl administration of thioridazine with fluoxetine or within a minimum of 5 weeks after fluoxetine has been discontinued coadministration of fluvoxamine with cisapride, thioridazine or pimozide concomitant use of thioridazine with paroxetine concomitant use of pimozide with sertraline coadministration of sertraline oral concentrate and disulfiram. 

Although behavioral treatments for social phobia have been well studied, there are very limited data on its pharmacological management, b- Blockers (propranolol, atenolol) have been recommended, but available evidence indicates their effect may be no different than that of placebo ( 78). In a controlled study, the monoamine oxidase inhibitor (MAOl) phenelzine has been shown to be more effective than placebo (78, 79). Anecdotal reports have also described efficacy with alprazolam, clonidine, and fluoxetine, but systematic data are lacking (80, 81, 82 and 83). 

A growing number of drugs are used that affect the many neurotransmitters in the brain benzodiazepines and others act on GABAergic transmission antidepressants, such as monoamine oxidase inhibitors and tricyclic antidepressants, are thought to increase the concentration of transmitter amines in the brain and so elevate mood—these will also act at peripheral nerve terminals, so interactions with them are a combination of peripheral and central actions. Levodopa (L-dopa) increases central as well as peripheral dopamine, and the newer class of psychoactive drugs, the selective serotonin reuptake inhibitors (SSRIs) of which the ubiquitous fluoxetine (Prozac) is best known, act in a similar way on serotonergic pathways. 

The depressive phase of manic-depressive disorder often requires concurrent use of an antidepressant drug (see Chapter 30). Tricyclic antidepressant agents have been linked to precipitation of mania, with more rapid cycling of mood swings, although most patients do not show this effect. Selective serotonin reuptake inhibitors are less likely to induce mania but may have limited efficacy. Bupropion has shown some promise but—like tricyclic antidepressants—may induce mania at higher doses. As shown in recent controlled trials, the anticonvulsant lamotrigine is effective for many patients with bipolar depression. For some patients, however, one of the older monoamine oxidase inhibitors may be the antidepressant of choice. Quetiapine and the combination of olanzapine and fluoxetine has been approved for use in bipolar depression. 

Newer antidepressants (eg, fluoxetine, paroxetine, citalopram, venlafaxine) are mostly SSRIs and are generally safer than the tricyclic antidepressants and monoamine oxidase inhibitors, although they can cause seizures. Bupropion (not an SSRI) has caused seizures even in therapeutic doses. Some antidepressants have been associated with QT prolongation and torsade de pointes arrhythmia. SSRIs may interact with each other or especially with monoamine oxidase inhibitors to cause the serotonin syndrome, characterized by agitation, muscle hyperactivity, and hyperthermia (see Chapter 16). 

A dangerous pharmacodynamic interaction may occur when fluoxetine or one of the newer selective serotonin reuptake inhibitors is used in the presence of a monoamine oxidase inhibitor. 

Stroll et al. (1994), from Harvard s McLean Hospital, compared the blinded charts of 49 consecutive inpatient admissions with antidepressant-induced mania with 49 matched cases of spontaneous mania over a 1-year period, from March 1, 1990, to February 28, 1991. The patients had been exposed to tricyclics (n = 19), fluoxetine (n = 13), monoamine oxidase inhibitors (n = 8), bupropion (n = 6), and mixed antidepressants (n = 3). (It is striking that these doctors were already aware of the risk of Prozac-induced mania approximately 2 years after the January 1988 introduction of Prozac into the market. Meanwhile, too many health care providers remain in denial about this significant risk.)... 

The symptoms described here resemble the 5HT toxicity syndrome (SEDA-25,16) and suggest that pethidine can provoke this reaction when combined with SSRIs, as it can with monoamine oxidase inhibitors. The report is also a useful reminder that the active metabolite of fluoxetine, norfluoxetine, has a half-life of about 1 week and would still have been present at the time of endoscopy, even though fluoxetine had been stopped 14 days before. 

The problem of the long half-life of fluoxetine, leading to interactions with monoamine oxidase inhibitors, even after withdrawal, has been discussed previously (SEDA-13, 12), and caused the manufacturer to circulate a warning to that effect. 

In the 1980s an entirely new class of antidepressant arrived with the SSRIs, firstly fluvoxamine immediately followed by fluoxetine (Prozac). Within 10 years, the SSRI class accounted for half of antidepressant prescriptions in the United Kingdom. Further developments in the evolution of the antidepressants have been novel compounds such as venlafaxine, reboxetine, nefazodone and mirtazapine, and a reversible monoamine oxidase inhibitor, moclobemide. 

A serious excitatory interaction between fluoxetine and pentazocine has been reported (SEDA-16, 89). The authors commented on the similarity of this syndrome to the reported dangerous interactions between monoamine oxidase inhibitors and narcotic analgesics, and suggested that increased central 5-HT activity may be the basis of the observed interaction. 

All SSRIs have common 5-HT agonistic effects and because of this, SSRIs have common interactions and side effects. SSRIs are potent inhibitors of serotonin reuptake by CNS neurons and may interact with other drugs such as monoamine oxidase inhibitors (MAOIs) or circumstances which cause serotonin release. A minimum 2 weeks wash-out period should be observed between stopping a MAOI and starting an SSRI. Conversely, a MAOI should not be started for at least 1 week after an SSRI has been stopped, 5 weeks after fluoxetine, and 2 weeks for paroxetine and sertraline. Escitalopram and citalopram are hypersensitive to each other. 

The bulk of literature examining antidepressant use in AD is made up of case reports and uncontrolled studies. Most of these report a favorable response to antidepressants, but several placebo-controlled trials have demonstrated mixed results. Of the antidepressants studied, citalopram, sertraline, clomipramine, and moclobe-mide (a monoamine oxidase inhibitor not marketed in the U.S.) were considered efficacious in at least one study but fluoxetine and imipramine were no better than placebo. It should be noted that citalopram and sertraline have both been studied in other placebo-controlled trials in this population with no difference over placebo. ... 

---