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Clomipramine (brand-name Anafranil®) is a tricyclic antidepressant. It was developed in the 1960s by the Swiss drug manufacturer Geigy (now known as Novartis) and has been in clinical use worldwide for decades.
Additional recommended knowledge
It may take 2 to 3 weeks before the full effects of this medication are noticed in all indications.
Along with SSRIs, clomipramine is a frequently prescribed drug for the treatment of OCD. As is typical with the older tricyclic antidepressants, it has more side effects than SSRIs, so some authorities regard it as a second-line treatment to be used if treatment with SSRIs fails. However, disregarding side effects, it may be slightly more effective in combatting the symptoms of OCD. It is not commonly used for treating depression, and usually another tricyclic (or drug from a different class) would be used. Clomipramine and the SSRIs (specifically Paroxetine) have also been used to treat premature ejaculation.
Clomipramine is the 3-chloro derivative of imipramine. Clomipramine is a strong, but not completely selective serotonin reuptake inhibitor (SSRI), as the primary active metabolite desmethylclomipramine acts preferably as norepinephrine reuptake inhibitor. Other hydroxy-metabolites are also active. α1 receptor blockage and β receptor downregulation as well as postsynaptic antagonism on histamine H1 receptors have been noted.
As with other tricyclics, downregulation of NMDA receptors may also account for its effects.
Clomipramine has the disadvantage of a higher incidence of seizures than seen with other tricyclic antidepressants (up to a dose of 250 mg daily in 0,5 %, more than 300 mg in 2 %).
Some studies have indicated that clomipramine is slightly more effective in the treatment of depression than other tricyclics.
Clomipramine may have a broad range of side effects:
Most of these side-effects are dose related and/or tolerance will develop with continued use.
Drug abuse and dependence
Clomipramine has no known potential for abuse and dependence. It is not a controlled substance.
Withdrawal symptoms occurring when clomipramine is stopped abruptly (agitation, fatigue, nausea, headaches, insomnia, sometimes activation of mania and rebound of depression or anxiety) is not indicative of dependence and can be avoided, if clomipramine is gradually withdrawn by reducing the daily dose by approximately 25% weekly. If medical reasons dictate an immediate termination of treatment, a short-term course of benzodiazepines (up to four weeks as needed) will usually suppress the unpleasant withdrawal symptoms.
Other reasons for caution
Depression itself can lead to thoughts or attempts of suicide. Emotionally unstable patients or those with suicidal thoughts should receive the smallest amount of the drug feasible. Often cotreatment with a sedative drug (e.g. a benzodiazepine or chlorprothixene) is necessary until remission of depression is evident.
Caution is advised when using clomipramine in the elderly, because they may be more sensitive to the effects of the drug (e.g., confusion may occur or worsen). Clomipramine should be used during pregnancy only if clearly needed. It is excreted into breast milk. The effects on the infant are not known at this time.
Clomipramine shows a number of clinical significant interactions, either due to central depressant or stimulant activity of the other drug or due to interference of the other drug with the metabolization and elimination of clomipramine or vice versa. Some examples are:
Initial doses are usually 25 mg 2 or 3 times daily or 75 mg once daily in slow released form. The dose may be increased in regular intervals (the usual dose per day is 100 to 225 mg). Doses up to 300 mg may be used, but these are associated with an increased risk of seizures. This medication may be taken with food to prevent stomach upset.
In hospitalized patients initial intramuscular injections and very slow intravenous infusions can be used, but the risk of hypotension and seizures may be increased with parental drug use. The advantage is that the onset of action may be faster.
Usually, clomipramine needs some weeks to reach its maximum effects and needs to be given as longterm treatment, sometimes for life (narcolepsy). Sometimes, in patients with narcolepsy the full effect of clomipramine is not sufficient. In these cases treatment with clomipramine should be terminated gradually and a commonly used central stimulant (e.g. modafinil, methylphenidate or methamphetamine) tried instead.
Clomipramine is not able to elevate the mood of non-depressive persons and any unindicated use may be dangerous.
If overdose is suspected, contact your local poison control center or emergency room immediately. United States residents can call the US national poison hotline at 1-800-222-1222. Other worldwide poison centers can be found at the World directory of poisons centers
Ten out of 12 patients presenting with manifest clomipramine overdose survived with appropriate treatment. These 10 patients took clomipramine doses of up to 5 grams. The 2 patients who died ingested 5.75 and 7 grams, respectively. Outside the US one patient died who took only 0.75 grams. Lethal doses may be lower, if other drugs have been taken in an overdose, too, particular central nervous depressants.
The symptoms and the treatment of an overdose are largely the same as for the other tricyclic antidepressants.
Clomipramine is widely used for the treatment of disturbed behaviour of dogs, cats, and horses. Marketed by Novartis for veterinary use under the name 'Clomicalm', clomipramine is given orally and is indicated for:
"Treatment of stereotypic behaviours (obsessive-compulsive disorders) in dogs such as acral lick dermatitis, excessive grooming and tail chasing. An aid in the treatment of anxiety disorders in dogs such as destructiveness, excessive vocalisation, loss of toilet control, associated with separation anxiety. An aid in the treatment of urine spraying in desexed and female cats." (Product Information for Clomicalm, Novartis Animal Health Australasia Pty Limited).
|This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Clomipramine". A list of authors is available in Wikipedia.|