Clomipramine dosage

A depressed man taking clomipramine 175 mg, levomepromazine 25 mg and flunitrazepam 2 mg daily, was started on lithium 600 mg daily. About one week later, after his dosage of lithium was raised to 1 g daily and he developed the serotonin syndrome (myoclonus, shivering, tremors, incoordination). Due to this reaction, and because his serum-lithium levels were 1.6 mmol/L, the lithium was stopped. The serotonin syndrome then abated. The clomipramine dosage was reduced, but some mild symptoms remained until the clomipramine was stopped. He responded well to lithium 600 mg daily alone, without developing the serotonin syndrome. ... 

A severe reaction, diagnosed as the serotonin syndrome, developed in a woman taking ademetionine shortly after her clomipramine dosage was raised. 

A 10-year-old boy has a 4-month history of fears of contamination and of refnsing food becanse there might be monster drool in it. He is begnn on clomipramine (CMl), initially 25 mg at night, and the dosage is gradnally increased to three times daily. He complains of mild confusion and dry mouth. A trough blood level of CMl and its demethylated metabolite reveal that CMl is 455 ng/mL and desmethyl CMl is 48 ng/mL. 

In a controlled multicenter study of 115 in-patients with relatively severe depression, moclobemide was better tolerated but had a weaker therapeutic effect than clomipramine. Nine of the patients taking moclobemide withdrew owing to worsening of depression and suicidality, although it is possible that the dosage of moclobemide (400 mg/day) was inadequate (SEDA-18, 15). 

Clomipramine, fluoxetine, sertraline, paroxetine, fluvoxamine, and citalopram are extensively metabolized in the Liver, and patients with significant liver disease should be prescribed these drugs cautiously and in lower doses than those used in healthy subjects. The pharmacokinetics of fluoxetine and fluvoxamine were similar in patients with renal faUme and in healthy subjects however, the manufacturer recommends starting with a lower dose in patients with renal impairment. The pharmacokinetics of sertraline are not altered in patients with significant renal dysfunction, and dosage adjustment is not necessary in these patients. Increased plasma concentrations of paroxetine occur in subjects with renal impairment. The initial dose of paroxetine should be reduced in patients with severe renal impairment, and upward titration should occm more slowly. No dosage adjustment is necessary for patients with mild to moderate renal impairment receiving citalopram. 

The interaction between clonidine and the trieyelics is established and clinically important. The incidence is uncertain but it is not seen in all patients. Avoid concurrent use unless the effects can be monitored. Increasing the dosage of clonidine may possibly be effective. The clonidine dosage was apparently successfully titrated in 10 out of 11 hypertensive patients already on amitriptyline or imipramine. Only clomipramine, desipramine and imipramine have been implieated so far, but other tricyclics would be expected to behave similarly (amitriptyline, nortriptyline and protriptyline have been shown to interact in animals ). The tetracyclic antidepressants maprotiline and mianserin do not generally appear to interact with clonidine. The isolated case of hypotension with trazodone is of unknown general importance. 

A number of other reports and studies clearly confirm that marked increases occur in the levels of amitriptyline, " clomipramine, desipramine, " imipramine " and nortriptyline, " accompanied by toxicity, if fluoxetine is added without reducing the dosage of the tricyclic antidepressant. Delirium and seizures have also been described, and a death has been attributed to chronic amitriptyline toxicity caused by fluoxetine. The pharmacokinetics of fluoxetine appear not to be affected by amitriptyline. ... 

The amitriptyline plasma levels of 8 patients rose (range 15 to 233%) when they were also given fluvoxamine 100 to 300 mg daily. Even larger rises in plasma clomipramine levels occurred (up to eightfold) in four other patients given fluvoxamine 100 to 300 mg daily. The trieyelie dosages remained the same or were slightly lower. No toxieity was seen. " ... 

Information seems to be limited to these reports. It would seem prudent to monitor for trieyolie adverse effeets (sueh as dry mouth, blurred vision and urinary retention) in patients given valproate and amitriptyline, clomipramine, or nortriptyline and to reduee the dosage of the tricyclic if necessary. Where possible eonsider monitoring tricyclic levels. Information about other trieyelie antidepressants seems to be lacking. The occurrence of status epileptieus in another patient reinforces the fact that the tricyclics can lower the eonvulsive threshold and should therefore be used with caution in patients with epilepsy. 

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