Tricyclic Antidepressants Depress Myocardial Function
Tricyclic antidepressants directly
depress human myocardial mechanical function in a dose-dependent manner
independent of effects on the cardiac conduction system, study results
show.
Tricyclic antidepressant (TCA) poisoning is responsible for more deaths
than any other prescription drug overdose and is often fatal, Dr. Heard
and colleagues note in the current issue of Academic Emergency Medicine
dated December 2001. "While the effects of TCA poisoning on the cardiac
conduction system are well described, the effects of TCAs on human
myocardial mechanical function is less well investigated," they write.
In in vitro experiments, Dr. Heard's team exposed human atrial tissue
obtained during cardiac bypass surgery to increasing doses of
desipramine and amitriptyline. After 30 minutes of exposure, desipramine
decreased myocardial "developed force" by 27%, 49%, and 74% at
concentrations of 0.4, 40, and 400 micrometers, respectively. For
amitriptyline, developed force fell by 38% and 89% at concentrations of
40 and 400 micrometers, respectively.
In contrast, untreated cultures retained 94% of baseline developed
force. The drug concentrations used are similar to serum levels achieved
during "serious TCA overdoses," the team notes.
"The major implication of our work is that TCA poisoning results in
impaired myocardial contractile function in addition to the previously
demonstrated slowing of intra-cardiac conduction," Dr. Heard said. "This
suggests that therapies directed solely at reversing dysrhythmias may
not be enough to reverse all of the observed effects in TCA-poisoned
patients."
Additional therapies aimed at reversing the direct cardiodepressive
effects of TCAs may improve outcome after TCA poisoning, the
investigators suggest.
Amitriptyline may be used in depressive illness of psychotic or
endogenous nature and in selected patients with neurotic depression.
Endogenous depression is more likely to be alleviated than are other
depressive states. Amitriptyline, because of its sedative action, is
also of value in alleviating the anxiety component of depression.
As with other tricyclic antidepressants, amitriptyline may precipitate
hypomanic episodes in patients with bipolar depression. These drugs
are not indicated in mild depressive states and depressive reactions.
Precautions
The potency of amitriptyline is such that addition of other
antidepressant drugs generally does not result in any additional
therapeutic benefit. Untoward reactions have been reported after the
combined use of antidepressant agents having varying modes of
activity. Accordingly, combined use of amitriptyline and other
antidepressant drugs should be undertaken only with due recognition of
the possibility of potentiation and with a thorough knowledge of the
pharmacology of both drugs. There has been no reports of untoward
events when patients receiving amitriptyline were changed immediately
to protriptyline or vice versa.
When amitriptyline is used to treat the depressive component of
schizophrenia, activation or aggravation of existing psychotic
manifestation may occur. Likewise, manic depressive patients may
experience hypomanic or manic episodes and hyperactive or agitated
patients may become overstimulated. Paranoid delusions, with or
without associated hostility, may be exaggerated. A reduction in dose
or discontinuation of amitriptyline may be indicated and
administration of a neuroleptic such as a phenothiazine, be considered
under these circumstances.
Seriously depressed patients should be carefully supervised. The
possibility of suicide in depressed patients remains during treatment.
Patients should not have access to large quantities of this drug
during treatment.