Clomipramine adverse effects

SSRIs are well tolerated. Adverse effects for compounds in this class include nervousness, tremor, dizziness, headache, insomnia, sexual dysfunction, nausea, and diarrhea. In addition, the tricycHc antidepressant clomipramine (33), which is a potent nonselective serotonin reuptake inhibitor, is approved for treatment of obsessive—compulsive disorder. 

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. 

Subsequent open-label studies of clomipramine have been published with mixed results and increased recognition of adverse effects. Clomipramine treatment of... 

All SSRIs have an antipanic effect. Their advantages are limited adverse effects and lack of toxicity. Because of more acceptable adverse effect profiles, the SSRIs are usually the drugs of choice. Several studies consistently indicate that SSRIs such as fluoxetine, sertraline, paroxetine, fluvoxamine, as well as agents such as clomipramine and trazodone, all possess antipanic efficacy, although the last may be less effective than imipramine ( 24, 105, 106, 107, 108 and 109). 

Adverse effects of various antidepressants are summarized in Table 30-5. Most common unwanted effects are minor, but they may seriously affect patient compliance the more seriously depressed the patient is, the more likely it is that unwanted effects will be tolerated. Most normal persons find that even moderate doses of many antidepressants cause disagreeable symptoms, especially the classic tertiary amine tricyclics amitriptyline, imipramine, clomipramine, and doxepin. With the SSRIs, transient nausea is the most frequent complaint, and decreased libido and sexual dysfunction create the greatest concerns during maintenance treatment. 

The adverse effects profile of fixed-dose clomipramine (150 mg/day) has been assessed in 112 hospitalized depressed patients (aged 22-70 years), of whom 38 were over 55 years of age (146). The only adverse effect that distinguished patients over 55 years was orthostatic hypotension older subjects had a significantly greater fall in systolic blood pressure on standing. Orthostatic hypotension can lead to falls and injuries, particularly in patients being... 

Clomipramine is the imipramine analogue of chlorproma-zine. However, while the difference between chlorproma-zine and promazine is large, adding a chloride atom to imipramine hardly affects its actions. Most trials have failed to show any superiority of the chlorinated compound over imipramine. The adverse effects profile is similar (1), but drowsiness, confusion, and feeling awful are commonly reported (2). 

In a controlled comparison between clomipramine and amitriptyline, the former caused adverse effects more often, especially drowsiness (3). Overdose toxicity is the same as with other tricyclic antidepressants (4) fatal interactions with monoamine oxidase (MAO) inhibitors have been reported (SEDA-18, 16 5). Altogether, toxic effects are not substantially different. 

The ability of SSRIs to cause delayed ejaculation has been used in controlled trials of men with premature ejaculation (61,62). Of the SSRIs, paroxetine and sertraline produced the most benefit in terms of increase in time to ejaculation, but fluvoxamine did not differ from placebo. Clomipramine was more effective than the SSRIs but caused most adverse effects. From a practical point of view many patients might prefer to take medication for sexual dysfunction when needed rather than on a regular daily basis, and it would be of interest to study the beneficial effects of SSRIs on premature ejaculation when used in this way. 

The adverse effects of moclobemide have been well reported in several studies, mainly comparisons of moclobemide with standard antidepressants. The consensus has been that moclobemide produces fewer anticholinergic effects and less orthostatic hypotension and dizziness than clomipramine or imipramine. The main problems... 

AMOXAPINE, CLOMIPRAMINE, DOXEPIN, IMIPRAMINE, NORTRIPTYLINE, TRIMIPRAMINE PROTEASE INHIBITORS Possibly t adverse effects of amoxapine with atazanavir and ritonavir Inhibition of CYP3A4-mediated metabolism of amoxapine, clomipramine and doxepin inhibition of CYP3A4-, CYP2D6-and CYP2C9-mediated metabolism of imipramine inhibition of CYP2D6-mediated metabolism of nortriptyline and trimipramine Monitor closely... 

Since the monoamine effects of tramadol resemble the effect of antidepressants, it has been compared with clomipramine + levomepromazine in patients with postherpetic neuralgia. The incidence of adverse effects was 77% with tramadol and 83% with clomipramine (SEDA-20, 81). 

Although several antidepressants are EDA-approved for use in children, only one, fluoxetine, is currently approved for childhood depression. Imipramine is approved for the treatment of enuresis, clomipramine for obsessive-compulsive disorder in children 12 years and older, and fluvoxamine along with fluoxetine is approved for obsessive-compulsive disorder in children. The treatment of depression in children remains challenging, as depression can be difficult to diagnose and treat once identified. The studies involving imipramine, sertraline, and fluoxetine found that the dose range and titration as well as adverse effects were similar to those in adults. " ... 

Most experts agree that the SSRIs are better tolerated than clomipramine. The SSRIs are less likely to cause cardiovascular, sedative, anticholinergic, and weight gain side effects. Clomipramine is less likely than the SSRIs to cause insomnia, akathisia, nausea, and diarrhea. Side effects may be more severe when larger doses are used and with faster dose escalation. Tolerance to adverse effects often develops over 6 to 8 weeks of treatment, and tolerance is more fikely to develop to nausea, diarrhea, sedation, diminished libido and/or orgasm, anxiety, restlessness, insomnia, and anticholinergic side effects than to akathisia. ... 

A double-blind crossover trial in which clomipramine was directly compared to haloperidol and placebo in 36 autistic adolescents and adults failed to demonstrate any advantages of clomipramine over haloperidol with respect to Aberrant Behavior Checklist (ABC) measures of hyperactivity and irritability. Although no serious adverse effects were reported, tolerability of clomipramine was significantly worse than haloperidol, with over half of the subjects being unable to complete the clomipramine phase of the study due to adverse effects and/or lack of efficacy. An open-label sfudy also reporfed a high frequency of adverse effects (Sanchez et al.. 

This can increase TCA serum levels (clomipramine and nortriptyline). Desipramine levels were not found to be impaired, although an additive adverse effect profile is evident (nausea, tremor, and tachycardia). 

Their in vitro potenoy for selectively inhibiting the 5-HT transporter more or less mirrors their clinical efficacy as SSRIs (11) paroxetine> sertraline> clomipramine> fluoxetine> citralopram> fluvoxamine> imipramine> amitriptyline> roboxetine> venlafaxine = milnacipran> desipramine. Clinically, however, all the SSRIs are equally effective over time, suggesting that these variations in potency do not affect efficacy or adverse effects. The SSRIs have less affinity for ai, 02, Hi, and musoarinic receptors, which may explain the adverse-effect profile differences between TCAs and SSRIs. 

The SSRIs are reported to have fewer side effects than the TCAs, which have strong anticholinergic and cardiotoxic properties (50). Among the SSRIs, there are few differences in adverse effects. The adverse effects observed for the SSRIs include nausea, diarrhea, anxiety, agitation, insomnia, and sexual dysfunction. Fewer patients have discontinued SSRIs than TCAs (amitriptyline and imipramine, and not nortriptyline, desipramine, doxepin, and clomipramine). 

Because doxepin is administered as an 85 15 mixture of geometric isomers, its mechanism of action and antidepressant properties refiects this ratio. Therefore, dioxepin s seiectivity for inhibiting presynaptic NE reuptake is most iikeiy caused by the 85% presence of the E-isomer in the geometric mixture. Its antidepressant activity is similar to amitriptyline. Data suggest NE reuptake inhibitory potency comparable to imipramine and clomipramine the fact that doxepin is an 85 15 mixture of - and Z-geometric isomers clouds its true efficacy for SERT or NET. The formation of N-desmethyIdoxepin results in inhibition of NE reuptake with enhanced noradrenergic activity. As a result of these mixed effects on the 5-HT and NE transporters, doxepin shares the pharmacological and adverse-effect profile of the other TCAs. 

Clomipramine is different from the other TCAs, exhibiting preferential selectivity for inhibiting the reuptake of 5-HT at the presynaptic neuronal membrane. Its antidepressant mechanism of action as an inhibitor of the 5-HT transporter is reduced in vivo, however, because of the formation of its active metabolite, N-desmethylclomipramine, which inhibits the reuptake of NE. As a result of its common structure with the other TCAs, clomipramine shares the pharmacological and adverse-effect profile of the other TCAs. 

However, 3 patients have developed the serotonin syndrome " and one developed agitation and eonfusion following the use of moclobemide and fluoxetine. A fatal case of the serotonin syndrome occurred in a patient who took an overdose of moclobemide, fluoxetine, and clomipramine, and another patient taking moclobemide developed the serotonin syndrome after taking an overdose of fluoxetine. A study suggests that the combination may cause a high rate of adverse effects (insomnia, dizziness, nausea and headache). ... 

A small study in healthy subjects found no problems when moclobemide was given 24 hours after clomipramine. However, the serotonin syndrome occurred in 3 patients when clomipramine was replaced by mo-clobemide without a washout period or with only a 24-hour washout period, " and in another patient when moclobemide was replaced by clomipramine after only 12 hours. A fatal case of the serotonin syndrome occurred in a patient taking clomipramine and amitriptyline, with symptoms manifesting within 30 minutes of a 300-mg dose of moclobemide. Two other patients developed fatal serotonin syndrome after taking moderate overdoses of moclobemide and clomipramine. The serotonin syndrome has been reported in at least 8 other cases of moclobemide and clomipramine overdose, one of which also involved tramadol (see also MAOIs + Opioids Tramadol, p.ll41), another fluoxetine (see also MAOIs or RIMAs + SSRIs, p.l 142), and yet another buspirone (see also MAOIs or RIMAs + Buspirone, p.l 133). Conversely, a case of an overdose of moclobemide and clomipramine resulted in no adverse effects except sinus tachycardia. ... 

Venlafaxine can cause a marked increase in the antimuscaiinic adverse effects of clomipramine, desipramine and nortriptyline. There are isolated reports of seizures in a patient taking venlafaxine and trimipramine and the serotonin syndrome has been seen in patients taking venlafaxine with, or shortly before, the use of tricyclics. 

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