As with other antidepressants (notably including selective serotonin reuptake inhibitors), it may paradoxically increase the risk of suicide in those under the age of 25, at least in the first few weeks of treatment.
[15][16] Common side effects include dry mouth, constipation, loss of appetite, sleepiness, weight gain, sexual dysfunction, and trouble urinating.
[7] Serious side effects include an increased risk of suicidal behavior in those under the age of 25, seizures, mania, and liver problems.
In a meta-analysis of various trials involving fluoxetine (Prozac), fluvoxamine (Faverin/Luvox), and sertraline (Zoloft) to test their relative efficacies in treating OCD, clomipramine was found to be significantly more effective.
It may, thus, be useful and of increased importance in any case for patients with a familial or personal history of epilepsy or seizures of some other kind to concurrently take a daily dose of an anti-convulsant drug (topiramate, gabapentin, etc.)
should they require or opt for treatment with an antidepressant which reduces the seizure-threshold significantly (bupropion, clomipramine, amoxapine, maprotiline, venlafaxine).
In the case of seizures occurring due to overdose of tricyclic antidepressants, intravenous lorazepam may successfully terminate them.
In certain cases of tremor, pindolol may be an especially sensible option for serious consideration, as there is substantial evidence that its utilisation is an effective augmentation-strategy for obsessive-compulsive disorder, an important indication for clomipramine.
Possible symptoms include: nausea, vomiting, abdominal pain, diarrhea, insomnia, headache, nervousness, anxiety, dizziness and worsening of psychiatric status.
[115][17][116] Probably all “anticholinergic” side-effects may be successfully reversed in a majority of people with bethanechol chloride,[117][118][119] although knowledge of this amenability has unfortunately decreased in medical circles over the decades.
Bethanechol supplementation arguably should, however, be seriously considered as an add-on treatment when tricyclics (which often carry significant anti-muscarinic effects, especially for amitriptyline, protriptyline, imipramine, and clomipramine) are prescribed, as it may alleviate potentially otherwise-limiting side-effects (blurry vision, dry mouth, urinary hesitancy/retention, etc.).
This practice can make drugs of otherwise indispensably potent value more tolerable to certain patients and spare them needless suffering, hence-reducing the overall side-effect burden or concern thereof.
[122] In accordance, occupancy of both the SERT and the NET has been shown with clomipramine administration in positron emission tomography studies with humans and non-human primates.
[115] Inhibition of muscarinic acetylcholine receptors is responsible for the anticholinergic side effects of clomipramine like dry mouth, constipation, urinary retention, blurred vision, and cognitive/memory impairment.
[115][17] On the other hand, sodium channel blockade is also thought to contribute to the analgesic effects of TCAs, for instance in the treatment of neuropathic pain.
[140][141] It achieves typical circulating concentrations that are similar in range to those of other TCAs but with an upper limit that is around twice that of amitriptyline and imipramine.
250 mg/d, as mentioned elsewhere, is the typical maximum recommended dose but some people may need as much as 300 mg/d or more to benefit from all clomipramine has to offer beyond its potent SNRI capacity alone.
[146] In contrast to other TCAs, studies have found that clomipramine and SSRIs, which are more selective SRIs, have similar effectiveness in the treatment of OCD.
[148][17][145] There is a case report of complete remission from OCD for approximately one month following a massive overdose of fluoxetine, an SSRI with a uniquely long duration of action.
In addition to serotonin reuptake inhibition, clomipramine is also a mild but clinically significant antagonist of the dopamine D1, D2, and D3 receptors at high concentrations.
[129][147][151] Addition of antipsychotics, which are potent dopamine receptor antagonists, to SSRIs, has been found to significantly augment their effectiveness in the treatment of OCD.
[147][152] As such, besides strong serotonin reuptake inhibition, clomipramine at high doses might also block dopamine receptors to treat OCD symptoms, and this could additionally or alternatively be involved in its possible effectiveness advantage over SSRIs.
[153][154] For this reason, it may also be that augmentation with neuroleptics (a common procedure in the occurrence of inadequate response to monotherapy with an SRI) is needed with less frequency with clomipramine relative to SSRIs, the latter of-which apparently lack significant activity as dopamine-receptor antagonists.
Although clomipramine is probably more effective in the treatment of OCD compared to SSRIs, it is greatly inferior to them in terms of tolerability and safety due to its lack of selectivity for the SERT and promiscuous pharmacological activity.
Caution, however, is generally prudent when doing this, as seizures, which are more likely to occur with clomipramine than every other tricyclic antidepressant besides maprotiline, become more and more of a risk beyond the normally-recommended upper-ceiling.
Some consider the minimum optimally-therapeutic dose of clomipramine in obsessive-compulsive disorder, which often requires much higher levels of serotoninergic concentration than other indications for these drugs, to be 200, rather than 150, milligrams per day.
Clomipramine is a tricyclic compound, specifically a dibenzazepine, and possesses three rings fused together with a side chain attached in its chemical structure.
[6] In fact, clomipramine was initially considered to be a "me-too drug" by the FDA, and in relation to this, was declined licensing for depression in the United States.
[6] As such, to this day, clomipramine remains the only TCA that is available in the United States that is not approved for the treatment of depression, in spite of the fact that it is a highly effective antidepressant.
[17] It remained the "gold standard" for the treatment of OCD for many years until the introduction of the SSRIs, which have since largely superseded it due to greatly improved tolerability and safety (although notably not effectiveness).