Clomipramine side effects profile

Antidepressants are used in the treatment of neuropathic pain and headache. They include the classic tricyclic compounds and are divided into nonselective nor-adrenaline/5-HT reuptake inhibitors (e.g., amitriptyline, imipramine, clomipramine, venlafaxine), preferential noradrenaline reuptake inhibitors (e.g., desipramine, nortriptyline) and selective 5-HT reuptake inhibitors (e.g., citalopram, paroxetine, fluoxetine). The reuptake block leads to a stimulation of endogenous monoaminer-gic pain inhibition in the spinal cord and brain. In addition, tricyclics have NMDA receptor antagonist, endogenous opioid enhancing, Na+ channel blocking, and K+ channel opening effects which can suppress peripheral and central sensitization. Block of cardiac ion channels by tricyclics can lead to life-threatening arrhythmias. The selective 5-HT transporter inhibitors have a different side effect profile and are safer in cases of overdose [3]. 

The tricyclic antidepressant clomipramine also has been studied for PMDD. In placebo-controlled trials, both continuous daily dosing and luteal phase administration proved effective.17 Compared with the SSRIs, however, clomipramine has a less desirable side-effect profile with low tolerability. 

In the event that the initial SSRI provides an unsatisfactory treatment response, preferred alternatives include (1) switching to another SSRI, (2) switching to ven-lafaxine or duloxetine, or (3) switching to clomipramine. Despite limited data to date regarding their efficacy, SNRls are included as alternatives prior to considering clomipramine due to their more favorable safety and side effect profiles. 

The study of TCAs in children with OCD led directly from the use of these medications in adults with similar symptoms. Findings have shown significant advantage with both CMI and DMI over placebo in the treatment of this illness (Flament et al., 1985 deVaugh-Geiss et al., 1992). Clomipramine is the only TCA with a distinct indication from the FDA for the treatment of OCD. Use of TCAs has recently been supplanted by selective serotonin reuptake inhibitor (SSRI) medications that may have a more favorable side effect profile. 

Because of their better side effect profile compared with clomipramine, including their lower propensity to decrease the seizure threshold, selective SRIs (SSRIs) have been receiving increasing attention as a treatment for the interfering symptoms associated with autistic disorder and other PDDs. 

The Food and Drug Administration (FDA) has approved clomipramine for the treatment of obsessive-compulsive disorder. Clomipramine is also used in the United States, Europe, Canada, England, and, indeed, most of the world as an antidepressant. In six random-assignment, double-blind studies, this agent was equal in efficacy to standard tricyclics, with a side-effect profile comparable with other TCAs ( Table 7-6). 

The selective serotonin reuptake inhibitors (SSRIs) are the first-line treatment of depression in the elderly. Compared with tricyciic antidepressants (TCAs), they are much safer in overdose and, for the most part, their side-effects are better tolerated. The antidepressants that have been shown, in controlled studies, to be effective in geriatric major depression are the SSRIs fluoxetine, paroxetine, and sertraline, the TCAs clomipramine and nortriptyline, and the serotonin and norepinephrine reuptake inhibitor (SNRi) venlafaxine. Given that most antidepressants are effective in the elderly, the choice of drug is based on its side-effect profile and its potential to interact with other medications. 

The traditional scheme is complicated by the fact that some antidepressants exhibit characteristics of more than one class. For example, clomipramine, a tricyclic antidepressant (TCA) with side effects and toxicity similar to other TCAs, works more like the selective serotonin reuptake inhibitors (SSRls). Similarly, venlafaxine and duloxetine, which are usually grouped with the atypical antidepressants, have a side effect and safety profile comparable to the SSRls. Although a classihcation system based on mechanism of action offers some advantage (see Table 3.7), even this scheme is limited by the fact that antidepressants that work in the same way may have widely divergent side effect and safety profiles. In the following discussion, the traditional classification system is adopted. Although fraught with problems and inconsistencies. 

Despite its considerable efficacy, clomipramine has given way to the SSRls as a result of their more favorable side effect and safety profiles. Clomipramine, however, is often used as an augmenfafion sfrategy for OCD pafienfs who are partial responders to SSRl therapy. The effectiveness of this approach has not been verified in confrolled frials. Furthermore, coadministration of clomipramine with some of the SSRls can result in potentially dangerous drug interactions. 

Indalpine is a non-tricyclic antidepressant with a serotonin selective profile. It is 6-7 times more potent than fluoxetine and clomipramine in inhibiting serotonin reuptake m vitro in rat brain synaptosomes. Statistically significant clinical effects within one week of onset of treatment have been reported. An anxiolytic effect may accompany the antidepressant effect. Indalpine appears devoid of anticholinergic and cardiovascular side effects and does not promote weight gain or affect appetite. 

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