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Chapter 29: Psychopharmacological Treatment
trials and once daily in the morning or the evening in the
adjunctive therapy trial.
3. In monotherapy trials, clinically relevant improvements were
observed beginning at doses in the range 0.05 to 0.08 mg/kg
once daily. Efficacy increased with increasing weight-
adjusted dose (mg/kg). If well tolerated, doses up to 0.12 mg/
kg once daily may provide additional benefit. Doses above
4 mg/day have not been systematically studied in controlled
clinical trials.
4. In the adjunctive trial, the majority of subjects reached opti-
mal doses in the 0.05 to 0.12 mg/kg/day range.
In clinical trials, there were dose-related and exposure-
related risks for several clinically significant adverse reactions
(e.g., hypotension, bradycardia, sedative events). Thus, consid-
eration should be given to dosing an extended-release prepara-
tion of guanfacine on a milligram-per-kilogram basis in order
to balance the exposure-related potential benefits and risks of
treatment.
Yohimbine
Yohimbine (Yocon) is an
a
2
-adrenergic receptor antagonist
that is used as a treatment for both idiopathic and medication-
induced erectile disorder. Currently, sildenafil (Viagra) and its
congeners and alprostadil (Impulse, Edex) are considered more
efficacious for this indication than yohimbine. Yohimbine is
derived from an alkaloid found in
Rubaceae
and related trees
and in the
Rauwolfia serpentina
plant.
Pharmacologic Actions
Yohimbine is erratically absorbed after oral administration, with
bioavailability ranging from 7 to 87 percent. There is extensive
hepatic first-pass metabolism. Yohimbine affects the sympatho-
mimetic autonomic nervous system by increasing plasma con-
centrations of norepinephrine. The half-life of yohimbine is 0.5
to 2 hours. Clinically, yohimbine produces increased parasym-
pathetic (cholinergic) tone.
Therapeutic Indications
Yohimbine has been used to treat erectile dysfunction. Penile
erection has been linked to cholinergic activity and to
a
2
-
adrenergic blockade, which theoretically results in increased
penile inflow of blood, decreased penile outflow of blood, or
both. Yohimbine is reported to help counteract the loss of sex-
ual desire and the orgasmic inhibition caused by some sero-
tonergic antidepressants (e.g., selective serotonin reuptake
inhibitors). It has not been found useful in women for these
indications.
Precautions
The side effects of yohimbine include anxiety, elevated BP and
heart rate, increased psychomotor activity, irritability, tremor,
headache, skin flushing, dizziness, urinary frequency, nausea,
vomiting, and sweating. Patients with panic disorder show
heightened sensitivity to yohimbine and experience increased
anxiety, increased BP, and increased plasma 3-methoxy-4-hydroxyphenylglycol (MHPG).
Yohimbine should be used with caution in female patients
and should not be used in patients with renal disease, cardiac
disease, glaucoma, or a history of gastric or duodenal ulcer.
Drug Interactions
Yohimbine blocks the effects of clonidine, guanfacine, and other
a
2
-receptor agonists.
Laboratory Interferences
No known laboratory interferences are associated with yohim-
bine use.
Dosage and Clinical Guidelines
Yohimbine is available in 5.4-mg tablets. The dosage of yohim-
bine in the treatment of erectile disorder is approximately 16 mg
a day given in doses that range from 2.7 to 5.4 mg three times
a day. In the event of significant adverse effects, dose should
first be reduced and then gradually increased again. Yohim-
bine should be used judiciously in psychiatric patients because
it may have an adverse effect on their mental status. Because
yohimbine has no consistent effect on erectile dysfunction, its
use remains controversial. Phosphodiesterase-5 (PDE-5) inhibi-
tors are the preferred medication for this disorder.
Prazosin
Prazosin (Minipress) is a quinazoline derivative and one of a
new chemical class of antihypertensives. It is an
a
1
-adrenergic
receptor antagonist as opposed to the drugs mentioned above,
which are
a
2
-blockers.
Pharmacologic Actions
The exact mechanism of the hypotensive action or prazosin is
unknown, particularly as it effects nightmare suppression. Pra-
zosin causes a decrease in total peripheral resistance that is
related to its action as an
a
1
-adrenergic receptor antagonist. BP
is lowered in both the supine and standing positions. This effect
is most pronounced on the diastolic BP. After oral administra-
tion, human plasma concentrations reach a peak at about 3 hours
with a plasma half-life of 2 to 3 hours. The drug is highly bound
to plasma protein. Tolerance has not been observed to develop
with long-term therapy.
Therapeutic Action
Prazosin is used in psychiatry to suppress nightmares, particu-
larly those associated with PTSD.
Precautions and Adverse Reactions
During clinical trials and subsequent marketing experience, the
most frequent reactions were dizziness (10.3 percent); headache
(7.8 percent); drowsiness (7.6 percent); lack of energy (6.9 per-
cent); weakness (6.5 percent); palpitations (5.3 percent); and
nausea (4.9 percent). In most instances, side effects disappeared
with continued therapy or have been tolerated with no decrease
