MAOIs Clomipramine

MAOIs TCAs-AMITRIPTYLINE CLOMIPRAMINE DESIPRAMINE IMIPRAMINE NORTRIPTYLINE t risk of stroke, hyperpyrexia and convulsions, t plasma concentrations of TCAs, with risk of toxic effects, t risk of serotonin syndrome and of adrenergic syndrome with older MAOIs. Clomipramine may trigger acute confusion in Parkinson s disease when used with selegiline TCAs are believed to also act by inhibiting the reuptake of serotonin and norepinephrine, increasing the risk of serotonin and adrenergic syndromes. The combination of TCAs and antidepressants can t risk of seizures Very hazardous interaction. Avoid concurrent use and consider the use of an alternative antidepressant. Be aware that seizures occur with overdose of TCAs just before cardiac arrest... 

Pharmacotherapy is also used to delay ejaculation. Initially, local anesthetic ointments were recommended, but later case reports and open trials described the beneficial effects of monoamine oxidase inhibitors (MAOIs), clomipramine, benzodiazepines, and selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine, paroxetine, and sertraline. 

In addition to this serious diet-drug interaction, irreversible MAOIs also potentiate the effects of sympathomimetic drugs like ephedrine found in over-the-counter cold remedies and recreational stimulants like amphetamine. The MAOIs also interact with drugs that increase synaptic concentrations of 5-HT, such as the tricyclic antidepressant clomipramine and the herbal SSRI antidepressant St John s wort (Hypericum spp.). The resulting serotonin syndrome is characterised by hyperthermia and muscle rigidity. While devoid of these side effects the reversible MAO-A inhibitor moclobemide has yet to establish itself as a first-line alternative to the SSRIs. 

Unfortunately, some patients respond poorly to these first-line interventions. In particular, patients with a long duration of illness, extreme agoraphobic avoidance, and comorbid personality disorders are more likely to exhibit a poor treatment response. For such patients, TCAs such as imipramine or clomipramine and MAOIs such as phenelzine remain viable strategies. 

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. 

Changing a patient from one MAOI to another, or to a TCA, requires a "wash-out" period of at least 2 weeks to avoid the possibility of a drug interaction. There is evidence to suggest that a combination of an MAOI with clomipramine is more likely to produce serious adverse effects than occurs with other TCAs. Regarding the newer non-tricyclic antidepressants, it is recommended that a "wash-out" period of at least 5 weeks be given before a patient on fluoxetine is given an MAOI this is due to the very long half-life of the main fluoxetine metabolite norfluoxetine. 

Serotonin syndrome Some TCAs inhibit neuronal reuptake of serotonin and can increase synaptic serotonin levels (eg, clomipramine, amitriptyline). Either therapeutic or excessive doses of these drugs, in combination with other drugs that also increase synaptic serotonin levels (such as MAOIs), can cause a serotonin syndrome consisting of tremor, agitation, delirium, rigidity, myoclonus, hyperthermia, and obtundation. 

Based on some intriguing case reports (Jenike et al. 1983), a trial with a monoamine oxidase inhibitor (MAOI) may be an option in OCD patients who have comorbid panic disorder. In a double-blind trial, both phenelzine and clomipramine were found to be effective in reducing symptoms in OCD, as reflected on two of four OC measures [Vallejo et al. 1992). None of the patients in this study had panic disorder. This study suggests that MAOIs may be helpful in some patients with OCD even in the absence of panic disorder. However, in an earlier comparison trial, clomipramine, but not the MAOI clorgiline, resulted in significant reduction in OC symptoms [Insel et al. 1983b). Additional studies are needed to evaluate the place of MAOIs (including the newer reversible inhibitors of monoamine oxidase A [RIMAs], such as moclobemide) in the pharmacotherapy of OCD. 

There are clear biological distinctions between OCD and PD. For example, panic attacks are produced by CO 2 inhalation, lactate infusion, yohimbine administration, psychostimulants, isoproterenol, and mCPP. By contrast, none of these agents except mCPP exacerbates obsessions or compulsions. Furthermore, OCD is benefited most by clomipramine or SSRIs, whereas panic attacks are helped by a variety of antidepressants (e.g., TCAs, SSRIs, MAOIs). 

MAOIs, TCAs, lithium, clomipramine (alone or with topical steroids), fluoxetine, and fluvoxamine may reduce the frequency and intensity of this disorder ( 210, 226, 255, 256, 257, 258, 259, 260 and 261) however, controlled trials are needed to conclusively establish efficacy. Relapse after initial improvement has also been reported, however. Data also indicate that both trichotillomania and OCD may respond to venlafaxine ( 262, 263). For children, such treatments should be reserved for only those with the more severe, refractory forms. 

Other options - a non-specific MAOI (e.g. phenelzine), RIMA (e.g. moclobemide), clomipramine. 

Use of MAOIs wifh clomipramine Is always prohibifed because of fhe risk of serofonin syndrome and deafh... 

Generally, do not use with MAO inhibitors, including f 4 days after MAOIs are stopped do not start an MAOl until 2 weeks after discontinuing clomipramine, but see Pearls... 

Unique among TCAs, clomipramine has a potentially fatal interaction with MAOIs in addition to the danger of hypertension characteristic of all MAOI-TCA combinations... 

A potentially fatal serotonin syndrome with high fever, seizures, and coma, analogous to that caused by SSRIs and MAOIs, can occur with clomipramine and SSRIs, presumably... 

Use of MAOIs with clomipramine is always prohibited because of the risk of serotonin syndrome and death... 

TCAs (especially imipramine and clomipramine)—contraindicated with MAOIs (trazodone may be used cautiously with MAOIs) Increased TCA levels s3mdrome of excitation, very high temperature, mania, seizures, coma, death... 

I MAOIs (especially clomipramine and tranylcypromine). I Antiepileptics (barbiturates decrease TCA levels). 

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