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Tricyclic antidepressants are used in numerous applications;
mainly indicated for the treatment of clinical depression,
neuropathic pain, nocturnal enuresis, and ADHD, but
they have also been used successfully for headache (including
migraine headache), anxiety, insomnia, smoking cessation,
bulimia nervosa, irritable bowel syndrome, narcolepsy,
pathological crying or laughing, persistent hiccups,
interstitial cystitis, and ciguatera poisoning, and
as an adjunct in schizophrenia.
Depression
For many years they were the first choice for pharmacological
treatment of depression. Although still considered effective,
they have been increasingly replaced by SSRIs and other
newer drugs. Newer antidepressants are thought to have
fewer side effects and are also thought to be less effective
if used in a suicide attempt, as the treatment and lethal
doses (see therapeutic index) are farther apart than
with the tricyclic antidepressants. Tricyclic antidepressants
are sometimes still used to treat refractory depression
that has failed to respond to standard SSRI therapy.
They are not considered addictive and are preferable
to the MAOIs. Side effects usually occur before depression
is effectively suppressed; for this reason and via other
mechanisms they can be dangerous, as volition may be
increased, giving the patient greater ability to attempt
suicide.
ADHD
Tricyclic antidepressants have been shown to be effective
in treating attention-deficit hyperactivity disorder.
ADHD is thought to be caused by dopamine and norepinephrine
shortages in the brain's prefrontal cortex. Tricyclic
antidepressants block the reuptake of these neurotransmitters,
thus acting as dopamine and norepinephrine agonists.
They are commonly used in patients for whom psychostimulants
(the primary medication for ADHD) are ineffective or
contraindicted. TCAs are more effective in treating
the behavioral aspects of ADHD than the cognitive deficits;
they help limit hyperactivity and impulsivity but have
little effect on attention.
Analgesia
Tricyclics are also known as effective analgesics for
different types of pain, especially neuropathic or neuralgic
pain (like back pain in radiculitis). A precise mechanism
for their analgesic action is unknown, but it is thought
that they modulate opioid systems in the CNS via an
indirect serotonergic route. Typically pain modification
requires lower dosages than for treating depression
(e.g. Amitriptyline at 10 to 30 mg rather than 75 to
150 mg). They are also effective in migraine prophylaxis,
but not in relief of an acute migraine attack. This
is also believed to be related to serotonergic effects.
There is, however, little evidence for an analgesic
effect in acute pain.
Nocturnal enuresis
Tricyclics with greater anti-muscarinic action (i.e.,
amitriptyline, imipramine and nortriptyline) may prove
useful in helping to treat nocturnal enuresis (bedwetting)
in children over the age of 7 years. The drug needs
to be gradually withdrawn and the total treatment period
is advised to be no greater than 3 months at a time.
It is thought that the anticholinergic effects of tricyclics
may inhibit urination, and/or the CNS stimulant effect
may lead to easier arousal when the stimulus of a full
bladder occurs. However, one robust review of tricyclics
for the treatment of enuresis found the benefits of
tricyclics were relatively small and transient and due
to potentially serious adverse effects suggested more
research into other methods (bedwetting alarms, behavioural
methods, desmopressin) which may be better suited for
treatment of this condition.
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