Clomipramine cardiovascular

Tricyclic drugs have, as the name implies, a three-ring structure, and interfere with reuptake of norepinephrine and/or serotonin into axon terminals. Tricyclic drugs include imipramine (Tofranil), amitriptyline (Elavil), clomipramine (Anafranil), and nortriptyline (Pamelor, Aventil). Tricyclics have the occasional but unfortunate cardiovascular side effects of arrhythmia and postural hypotension. Newer, nontricyclic antidepressants have been developed that are collectively referred to as SSRIs. These have a potent and selective action on serotonin, and lack the cardiovascular side effects of the tricyclics. These include fluoxetine (Prozac), paroxetine (Paxil), sertraline (Zoloft), and fluvoxamine (Luvox). A fifth SSRI, citalopram (Celexa) has been used in Europe and has recently been approved in the United States. Venlafaxine (Effexor) blocks reuptake of norepinephrine and serotonin, while bupropion (Wellbutrin) acts on both dopamine and norepinephrine. 

This chapter describes the structure and neurochemical function of TCAs, metabolism and significant interactions with other medications, side effects, and specific recommendations for monitoring of side effects in children and adolescents. Because of the recent concern regarding the sudden deaths of children stabilized on TCAs, particular attention will be paid to the potential cardiovascular effects of these medications. The chapter will focus on the five TCA medications that have been most widely used in children amitriptyline (AMI), nortriptyline (NT), imipramine (IMI), desipratnine (DMI), and clomipramine (CMI). 

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. ... 

Rare Hepatic toxicity tinnitus bone marrow depression, including agranulocytosis seizures peripheral neuropathy severe cardiovascular effects in patients with cardiac disease photosensitivity dysarthria smttering withdrawal symptoms nausea, tremor, anorgasmia, and seizures may be more common with clomipramine tardive dyskinesia and neuroleptic malignant syndrome with amoxapine renal failure with overdosage of amoxapine... 

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. 

---