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Chapter 29: Psychopharmacological Treatment
The use of trazodone is contraindicated in pregnant and
nursing women. Trazodone should be used with caution in per-
sons with hepatic and renal diseases.
Drug Interactions
Trazodone potentiates the CNS depressant effects of other cen-
trally acting drugs and alcohol. Concurrent use of trazodone and
antihypertensives may cause hypotension. No cases of hyper-
tensive crisis have been reported when trazodone has been used
to treat MAOI-associated insomnia. Trazodone can increase
levels of digoxin and phenytoin. Trazodone should be used
with caution in combination with warfarin. Drugs that inhibit
CYP3A4 can increase levels of trazodone’s major metabolite,
mCPP, leading to an increase in side effects.
Laboratory Interferences
No known laboratory interferences are associated with the
administration of trazodone.
Dosage and Clinical Guidelines
Trazodone is available in 50-, 100-, 150-, and 300-mg tablets.
Once-a-day dosing is as effective as divided dosing and reduces
daytime sedation. The usual starting dose is 50 mg before sleep.
The dosage can be increased in increments of 50 mg every
3 days if sedation or orthostatic hypotension does not become a
problem. The therapeutic range for trazodone is 200 to 600 mg a
day in divided doses. Some reports indicate that dosages of 400
to 600 mg a day are required for maximal therapeutic effects;
other reports indicate that 250 to 400 mg a day is sufficient.
The dosage may be titrated up to 300 mg a day; then the per-
son can be evaluated for the need for further dosage increases
on the basis of the presence or the absence of signs of clinical
improvement.
Once-daily trazodone is available as bisectable tablets of
150 mg or 300 mg. The starting dosage of the extended-release
formulation is 150 mg once daily. It may be increased by 75 mg
per day every 3 days. The maximum dosage is 375 mg per day.
Dosing should be at the same time every day in the late evening,
preferably at bedtime, on an empty stomach. Tablets should be
swallowed whole or broken in half along the score line.
R
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▲▲
29.24 Opioid Receptor
Agonists
Opioid receptor agonists are a structurally diverse group of
compounds that are used for pain management. These drugs
are also called narcotics. Although highly effective as analge-
sics, they often cause dependence and are frequently diverted
for recreational use. Commonly used opioid agonists for pain
relief include morphine, hydromorphone (Dilaudid), codeine,
meperidine (Demerol), oxycodone (OxyContin), buprenorphine
(Buprenex), hydrocodone (Robidone), tramadol (Ultram), and
fentanyl (Durogesic). Heroin is used as a street drug. Metha-
done is used both for pain management and for treatment of
opiate addiction. This chapter focuses on the
m
-opioid receptor
agonists that are most likely to be used in the treatment of psy-
chiatric disorders instead of pain management.
It is now recognized that the pharmacology of the opioid sys-
tem is complex. There are multiple types of opioid receptors,
with
m
- and
k
-opioid receptors representing functionally oppos-
ing endogenous systems (Table 29.24-1). All of the compounds
above, which represent the most extensively used narcotic anal-
gesics, are agonists at
m
-opioid receptors. However, analgesic
effects also result from antagonist effects on the
k
-opioid recep-
tor. Buprenorphine has mixed receptor effects, being primarily a
m
-opioid receptor agonist as well as a
k
-opioid antagonist.
There is growing interest in the use of some drugs that act on
opioid receptors as alternative treatments for a subpopulation of
patients with refractory depression, as well as treatment for cut-
ting behavior in patients with borderline personality disorder.
Consideration of such off-label use is tempered by the well-
known fact that ongoing, regular use of opioids produces depen-
dence and tolerance and may lead to maladaptive use, functional
impairment, and withdrawal symptoms. The prevalence of
