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APPENDIX
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ABLE 20–A. Findings from published studies of deep brain stimulation (DBS) targets for treatment-resistant
T
depression (continued)
362
Target and
reference
Nucleus accumbens
Millet et al.
2014
Bewernick
et al. 2012
Bewernick
et al. 2010
6 included,
4implanted
Maximum Response Remission
End follow-up Comment on
N of study reported Definition Rate (%) Definition Rate (%) Sample study design
15 months 15 months ≥50%
11 12 months 12 months to
4years
10
12 months 12 months ≥50%
reduct ion in
score
≥50%
reduct ion in
score
reduct ion in
score
5 months: 0 HAMD-17
9 months: 0 9 months: 0
15 months: 50 15 months: 25
12 months: 45.5 HAMD-28
Last follow-up:
45.5
12 months: 50 HAMD-28
score ≤7
score ≤10
score ≤10
5 months: 0 — Crossover to
12 months: 9 Slightly
Last follow-
up: 9
Time point
NA: 30
caudate stimulation
at 5 m onths (until
month 9) in case
of nonresponse to
nucleus accumbens
stimulation;
multicenter pilot
study
Long-term
extended
sampl e
(+ 1 patient)
of Bewernick
et al. 2010
— Pilot study
follow-up
The APA Publishing Textbook of Mood Disorders, Second Edition
APPENDIX
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ABLE 20–A. Findings from published studies of deep brain stimulation (DBS) targets for treatment-resistant
T
depression (continued)
Vagus Nerve Stimulation and Deep Brain Stimulatio
Target and
reference
Superolateral branch of the medial forebrain bundle
Davidson
et al. 2020
Coenen et al.
2019
Fenoy et al.
2018
Bewernick
et al. 2017b
N of study reported Definition Rate (%) Definition Rate (%) Sample study design
16 12 months 12 months
End follow-up Comment on
2 6 months 8 months ≥ 50%
6 12 months 12 months
8 12 months 4 years ≥50%
Maximum Response Remission
reduct ion in
score
≥50%
reduction
in MADRS
score
≥50%
reduction
in MADRS
score
reduction
in MADRS
score
Any time point: 0
12 months:
100 (of all
patients)
12 months: 66.7 HAM-D
12 months: 75 MADRS
Last follow-up:
87.5 (area
under the
curve)
NA NA —
MADRS
score ≤10
score <7
score <10
12 months:
50 (of all
patients)
12 months:
66.7
12 months:
50
—
Slightly
extended
sampl e
(+2 patients)
of Fenoy
et al. 2016
Slightly
extended
sampl e
(+1 patient)
of Schlaepfer
et al. 2013
6 months of open-
lab el stimulation
followed by 2 ×2
weeks of doubleblind OFF/ON
Blinded stimulation
for 8 wee ks;
staggered onset
Long-term
follow-up
Long-term
follow-up
363
APPENDIX
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ABLE 20–A. Findings from published studies of deep brain stimulation (DBS) targets for treatment-resistant
T
depression (continued)
364
Target and
reference
Superolateral branch of the medial forebrain bundle (continued)
Fenoy et al.
2016
Schlaepfer
et al. 2013
Single case studies are not reported.
ALIC = anterior limb of the internal capsule; BDI= Beck Depression Inventory; BNST=bed nucleus of the stria terminalis; HAM-D=Hamilton Rating Scale for Depression
(HAMD-17, HAMD-24, and HAMD-28=17-item, 24-item, and 28-item HAM-D, respectively); ITP=inferior thalamic peduncle; MADRS=Montgomery-Åsberg Depression
Rating Scale; NA=not available; RCT=randomized controlled trial.
Source. Adapted from eTable (
sive Brain Stimulation in the Treatment of Psychiatric Illness—Proposed Indications and Approaches.” Deutsches Ä? rzteblatt International 118(3):31–36, 2021. Available at:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8129059/. Accessed January 7, 2022.
Table data based on reviews by Dandekar et al. 2018, Drobisz and Damborská 2019, and Kisely et al. 2018 with updates.
N of study reported Definition Rate (%) Definition Rate (%) Sample study design
End follow-up Comment on
4 12 months 6 months ≥50%
reduction
in MADRS
score
7 3 months 3–8 months ≥ 50%
reduction
in MADRS
score
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8129059/table/T2/) in Schlaepfer TE, Meyer-Lindenberg A, Synofzik M, et al.: “Inva
1 week: 75 NA NA — Single-blind sham
6 months: 50
1 week: 57.1 MADRS
3 months: 85.7 3 months: 57.1
Last follow-up:
85.7
score <10
1 week: 42.9 — Pilot study
Last follow-
up: 57.1
stimulation for
4 weeks; interim
report
Maximum Response Remission
The APA Publishing Textbook of Mood Disorders, Second Edition
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CHAPTER 21
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Other Antidepressants
Bupropion, Mirtazapine, and Trazodone
Charles DeBattista, M.D.
Bupropion, mirtazapine, and trazodone represent pharmacologi-
cally unique antidepressants that do not fit neatly into other common antidepressant
classes, such as the selective serotonin reuptake inhibitors (SSRIs), serotonin-norepi
nephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), and monoamine oxidase inhibitors (MAOIs). Each of these three drugs has found important
clinical niches in the treatment of depression, whether used as monotherapies or as
adjunctive agents in combination with other antidepressants. Bupropion and mirtazapine are commonly co-prescribed with SSRIs and SNRIs to augment antidepressant
response, while trazodone has become among the more common agents prescribed
for insomnia. The unique pharmacology of these drugs also makes them among the
least likely antidepressants to be associated with sexual side effect. Although trazodone, mirtazapine, and bupropion have been available for decades, they remain
important and widely prescribed agents in the treatment of depression.
-
Bupropion
Bupropion became of interest to medicinal chemists in the 1960s, when it was found
to have antidepressant properties in screening tests but did not appear to have some
of the downsides of the TCAs and the MAOIs. Bupropion has been available to clinicians in the United States since 1986, but its mechanism of action is still not completely understood. Among its distinct properties relative to most currently available
antidepressants is that bupropion does not have serotonergic properties. It is not a
significant inhibitor of the serotonin (5-hydroxytryptamine [5-HT]) transporter and
does not act on serotonin type 2 (5-HT
) or type 1A (5-HT1A) receptors (Costa et al.
2
365
366 The APA Publishing Textbook of Mood Disorders, Second Edition
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2019; Foley et al. 2006). This lack of serotonergic effects contributes to bupropion’s
low proclivity for causing sexual side effects (Pereira et al. 2014).
Bupropion’s primary mechanism of action appears to be on the norepinephrine
system (Khan et al. 2016), where it reduces the excretion of norepinephrine and its
metabolites. Its active metabolites, including hydroxybupropion and erythrobupro
pion, inhibit the norepinephrine transporter, although less potently than most TCAs
and SNRIs (Costa et al. 2019). Bupropion does appear to downregulate β-adrenergic
receptors in the locus coeruleus, and chronic administration of bupropion is known
to modestly inhibit tyrosine hydroxylase activity.
Although often characterized as a dopaminergic drug, bupropion’s dopamine
properties are less evident than its noradrenergic effects. For example, animal studies
have reported that it increases dopamine concentrations in the nucleus accumbens
and mildly inhibits dopamine reuptake, but human studies have been less consistent.
Human PET studies have not demonstrated a significant effect of bupropion on the
dopamine transporter (Meyer et al. 2002). In addition, the major metabolite of dopa
mine, homovanillic acid, does not appear to be significantly affected by bupropion
administration (Goodnick et al. 1998).
Because if its noradrenergic and perhaps some dopaminergic effects, bupropion is
an activating antidepressant commonly prescribed for patients with major depressive
disorder (MDD) whose depression is characterized by fatigue, hyperphagia, and
hypersomnia rather than patients with significant insomnia, anxiety, and anorexia
(Jefferson 2008; Patel et al. 2016). Bupropion is also among the more common augmen
tation strategies used by clinicians to improve the antidepressant effect of SSRIs,
SNRIs, and other antidepressants. Despite the popularity of bupropion augmentation,
few placebo-controlled trials have ever been completed with this strategy. However,
bupropion augmentation has been examined in several large, randomized comparative efficacy studies, including the Sequenced Treatment Alternatives to Relieve Depression (STAR*D; Trivedi et al. 2006) and the Veterans Affairs Augmentation and
Switching Treatments for Improving Depression Outcomes (VAST-D; Mohamed et al.
2017). In general, these studies have concluded that bupropion is about as useful as
other augmenting agents, such as buspirone and aripiprazole, but not superior to
them. Some open-label studies have suggested that adding bupropion to a serotoner
gic antidepressant can mitigate antidepressant-induced sexual side effects, but controlled studies have not been conclusive in this regard.
Bupropion is the only antidepressant with a specific indication for prevention of
depressive episodes associated with seasonal affective disorder (SAD). Three registration trials with a total of 1,100 patients with SAD who were treated with bupropion
extended-release demonstrated that an average dosage of 300 mg/day started in the
fall was significantly more effective than placebo in preventing the recurrence of depression (Niemegeers et al. 2013). Subsequent analyses have shown that bupropion
has a number needed to treat of 5 for preventing recurrences of depression in patients
with SAD who have frequent recurrences.
In addition to the treatment of depression, bupropion has been FDA approved for
two other indications. One indication is in the aid of smoking cessation. Registration
trials and subsequent studies indicate that patients with nicotine dependence who
were treated with 150–300 mg/day were more likely to abstain from smoking than
those treated with placebo (Goldstein 1998; Jorenby 2002). The other approved indi-
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367 Other Antidepressants: Bupropion, Mirtazapine, and Trazodone
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cation is weight loss when used in a combination pill with naltrexone. Overweight or
obese subjects who took the combination of bupropion and naltrexone for up to 56
weeks lost an average of 5% of their body weight, compared with approximately 3%
of those given placebo (Greig and Keating 2015; Onakpoya et al. 2020). Off-label uses
of bupropion for which there is some empirical support include the treatment of
ADHD, persistent depressive disorder (dysthymia), and bipolar depression (in combi
nation with a mood stabilizer). Unlike most antidepressants, bupropion has not consistently demonstrated benefit in the treatment of anxiety disorders, although some
small positive studies in the treatment of social anxiety disorder have been reported.
Because bupropion is primarily metabolized via the cytochrome P450 (CYP) 2B6
isoenzyme, which is not involved in the metabolism of most medications, the risk of
pharmacokinetic drug interactions is relatively small (Costa et al. 2019; Jefferson et al.
2005). Bupropion is a mild to moderate inhibitor of CYP2D6 and may interfere with
the metabolism of substrates of this enzyme, although such interactions are rarely
clinically significant. The most significant drug interaction may be with an MAOI,
which may increase the risk of a hypertensive crisis (although not a serotonin syn
drome). Drugs that lower the seizure threshold might also further increase the risk of
seizure associated with bupropion.
Bupropion has a favorable side-effect profile in comparison with many other antidepressants (Saiz Ruiz et al. 2011). Because of its lack of serotonergic activity, it is less
likely to be associated with sexual side effects. It does not induce orthostatic hypotension, and weight gain is uncommon. No significant anticholinergic side effects are
associated with bupropion; dry mouth does occur but is thought to be related to the
noradrenergic properties of the drug. The primary side effects are those associated
with CNS activation. Bupropion is associated with worsening insomnia and should
not be taken close to bedtime. It is not anxiolytic, and some anxious patients report an
increase in anxiety and agitation with the drug. Likewise, bupropion can increase irritability in some patients. Increases in blood pressure and heart rate can occur. About
21% of patients in the MDD trials experienced some tremor with bupropion, which
was about three times the rate of tremor seen in patients given placebo.
The most serious adverse event associated with bupropion is seizure (Davidson
1989), which is primarily associated with the immediate-release formulation. Seizure
incidence is estimated at approximately 0.4% (4/1,000) for dosages less than or equal
to 450 mg/day, with risk increasing substantially for dosages greater than 450 mg/
day (i.e., up to 4.0% [4/100]). The seizure risk for the sustained- and extended-release
formulations has been estimated at 0.1% (1/1,000), which is similar to the risk associated with other antidepressants.
-
-
Mirtazapine
Mirtazapine was synthesized in 1989 and approved in the United States in 1996 for
the treatment of MDD. Mirtazapine is pharmacologically unique because it is not a
monoamine reuptake inhibitor but has some noradrenergic and serotonergic receptor
effects (Nutt 1997). For example, it is a presynaptic α
in the presynaptic release of norepinephrine. The increase in norepinephrine in the
synapse concurrently result in an increase in serotonergic neurotransmission via
receptor antagonist that results
2
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stimulation of α
does not block α
tazapine is also an antagonist of the serotonin 5-HT
the histamine H
receptors on serotonin neuron cell bodies. However, mirtazapine
1
receptors and is not associated with inducing hypotension. Mir-
2
and 5-HT3 receptors, as well as
2
receptor.
1
In clinical trials, mirtazapine appears to be effective for both outpatients with
milder depression and more severely ill inpatients with MDD. Early efficacy trials in
MDD concluded that mirtazapine was as effective as the TCAs doxepin and amitrip
tyline (Mathur et al. 2002; Montgomery et al. 1998). In addition, mirtazapine appears
in clinical trials to be as effective as various SSRIs, including paroxetine, fluoxetine,
and citalopram (Thompson 1999). In some of these trials, mirtazapine had more rapid
anxiolytic and antidepressant properties (Fawcett and Barkin 1998).
Mirtazapine has been used to treat common subtypes of depression. Some studies
suggest that it is both effective and well tolerated in patients with geriatric depression
(Bradley et al. 2016; Holland and Bhogle 2013). Side effects that can be problematic in
some patients, including sedation and weight gain, may be desirable in some geriatric
patients. In addition, studies have shown efficacy in the treatment of other subtypes
of depression, including brief recurrent, atypical, and seasonal depression (Stahl et al.
1997).
In addition to its use in the monotherapy of depression, mirtazapine is frequently
combined with other antidepressants to augment response. In the STAR*D trial, the
combination of mirtazapine and venlafaxine was as effective as switching to an MAOI,
tranylcypromine, and better tolerated in the treatment of patients with MDD whose ill
ness had failed to respond to three consecutive antidepressant treatments (Trivedi et
al. 2006). Still, only 13% of the subjects treated with a combination of venlafaxine and
mirtazapine achieved a remission-level response in the STAR*D trial. Most but not all
studies have found that adding 15–30 mg/day of mirtazapine to an SSRI or SNRI is
effective in augmenting antidepressant response. However, the largest randomized
controlled trial (RCT) conducted to date (Kessler et al. 2018) examined the efficacy of
adding mirtazapine or placebo to SSRI or SNRI treatment in 480 primary care patients
with MDD whose illness had not responded to monotherapy. No statistical advantage
was found for adding mirtazapine over adding placebo. Likewise, the Combining
Medications to Enhance Depression Outcomes trial (Rush et al. 2011), which examined
the efficacy of combining mirtazapine with venlafaxine at the onset of MDD treatment,
found no advantage over monotherapy in achieving response or remission.
Although mirtazapine is approved only for the treatment of MDD, there is reason
to believe that the drug is beneficial in the treatment of some anxiety disorders
(Gambi et al. 2005; Leinonen et al. 1999; Muehlbacher et al. 2005). Small and openlabel studies have suggested some benefit for monotherapy with mirtazapine or for
its use as an adjunctive agent in the treatment of social anxiety disorder, generalized
anxiety disorder, and PTSD (Gambi et al. 2005; Muehlbacher et al. 2005; Ribeiro et al.
2001; Schneier et al. 2015). Among the most common uses of mirtazapine beyond the
treatment of MDD is in the treatment of insomnia. Along with trazodone and quetiapine, mirtazapine is frequently used as a non-habit-forming strategy for the treatment
of insomnia. Low dosages of mirtazapine (7.5 mg/day) were found to be as effective
as 50 mg/day of quetiapine in a controlled trial of 19 healthy men with transient insomnia (Karsten et al. 2017), and mirtazapine increased total sleep time by 30 minutes
and reduced awakenings by 40%. Studies of mirtazapine in the treatment of insomnia
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369 Other Antidepressants: Bupropion, Mirtazapine, and Trazodone
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in patients with MDD, as well as in those with cancer, have indicated efficacy in improving sleep (Economos et al. 2020; Theobald et al. 2002).
Nonpsychiatric uses of mirtazapine include the treatment of pain syndromes and
nausea. Mirtazapine, as a mixed serotonergic/adrenergic agent, has shown benefit in
the treatment of pain disorders such as fibromyalgia. Several small, open-label and
controlled studies have found it to be effective in the treatment of fibromyalgia with
and without concomitant depression (Ottman et al. 2018; Welsch et al. 2018). Its 5-HT
receptor antagonist effects have found a role in the treatment of nausea and reduced
appetite in patients with cancer, as well as in the pre- and postoperative management
of nausea and anxiety in surgery patients (Chang et al. 2010; Kim et al. 2008).
The primary drug interactions with mirtazapine are pharmacodynamic rather pharmacokinetic. Although mirtazapine is partially metabolized via CYP2D6 and CYP3A4,
potent inhibitors of these isoenzymes, such as paroxetine and ketoconazole, have mod
est and clinically insignificant effects on mirtazapine blood levels (Jaquenoud Sirot et
al. 2012; Sitsen et al. 2001). On the other hand, the sedating effects of mirtazapine can
be enhanced by the concomitant administration of CNS depressants, including alcohol, benzodiazepines, and most hypnotic drugs. Its α
effects have been associated
2
with inducing a hypertensive crisis when used in combination with an MAOI (Ubogu
and Katirji 2003). Thus, mirtazapine should be stopped at least 2 weeks before MAOI
treatment begins.
3
-
somnolence, dry mouth, and weight gain (Nutt 2002; Watanabe et al. 2010). More
than half of patients taking mirtazapine experience somnolence, so it is generally
taken at night. A counterintuitive effect is that lower dosages may be associated with
more sedation than higher dosages. At a dosage of less than 15 mg/day, mirtaza
pine’s antihistamine effects predominate over its noradrenergic and serotonergic actions (Shuman et al. 2019). Thus, patients experience more sedation at 7.5 mg/day
than at 30 mg/day. On the other hand, most patients do not find 30 mg/day any more
sedating than 15 mg/day. Many patients with MDD find the sedating effects to be
useful in treating insomnia; however, few find the other major side effect, weight
gain, to be as useful. The exceptions are patients who have lost weight secondary to
their MDD, patients with a low BMI at baseline, and some geriatric patients. As mentioned, patients with cancer have sometimes benefited from the antinausea and appetite-increasing effects associated with mirtazapine. In MDD studies, mirtazapine was
associated with a greater than 7% increase in body weight in approximately 7.5% of
patients, and at least 20% of patients gained weight on the drug (PDR Staff 2017).
Mirtazapine is known to increase cholesterol and triglyceride levels in some patients. In premarketing studies, 15% of patients had an increase of more than 20% in
cholesterol levels, and about 6% of patients had a significant increase in triglyceride
levels (PDR Staff 2017). Statin agents appear to be effective in treating mirtazapineassociated increases in cholesterol and triglycerides. Postural hypotension is seen in
about 7% of patients taking mirtazapine. This risk is higher in older patients and
those taking antihypertensives but rarely is a basis for discontinuing the drug.
In contrast to most antidepressants, sexual side effects are not common with mirtazapine (Clayton et al. 2014). In fact, many patients who have antidepressantinduced sexual side effects have a resolution of these side effects when switched to
mirtazapine.
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370 The APA Publishing Textbook of Mood Disorders, Second Edition
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Tra z odone
Trazodone was the first alternative to the TCAs and MAOIs that was a serotoninspecific antidepressant. Introduced in the United States in 1981, it was considered a
safer alternative to the older agents and was very popular among clinicians until other
safe and easy-to-use agents, such as the SSRIs, became available later in the 1980s.
Trazodone is a postsynaptic 5-HT
5-HT
receptor interacts with the other receptors in the serotonin family, including the
2
5-HT
receptor, which appears to be important in the pathophysiology of both anxi-
1A
ety and depression. In addition, trazodone is a modest serotonin transporter inhibitor
and an α
-adrenergic receptor antagonist. It also inhibits the H1 receptor, which con-
1
tributes to its sedating properties.
The only FDA indication for trazodone is in the treatment of MDD. Many clinicians
regard it as a less efficacious antidepressant than the TCAs or other antidepressants,
particularly in patients with more serious depression. However, reviews of comparison
studies have generally not found a significant difference in efficacy between trazodone
and the TCAs or other antidepressants (Patten 1992; Yi et al. 2018). Many dozens of
RCTs have been published since the 1970s demonstrating the efficacy of trazodone in
the treatment of MDD. Early studies tended to employ more aggressive dosing, often
reaching the target dosage of 300–600 mg/day in the first week. This rapid titration was
often poorly tolerated because of the drug’s sedative effects. Most but not all patients
are able to tolerate a more gradual titration of the drug. Given the large number of other
antidepressant choices that do not require a slow titration and are not as sedating, trazodone is used less commonly in the treatment of MDD now than it once was.
The most common off-label use of trazodone is in the treatment of insomnia. Trazodone, like mirtazapine, is a non-habit-forming alternative to traditional benzodiazepines and related hypnotic drugs. However, despite its popularity as a sleeping agent,
very little research has been done on the utility of trazodone in the treatment of pri
mary insomnia (Jaffer et al. 2017). Doses of 50–100 mg given 30 minutes before bedtime appear to reduce sleep latency and result in fewer awakenings. However, trazodone is also associated with small but significant worsening of daytime cognitive
function, including verbal learning and short-term memory. It appears to be a useful
adjunct in the treatment of insomnia associated with depression (Jindal 2009) and
perhaps Alzheimer’s disease (Camargos et al. 2014), but is less useful for primary insomnia and insomnia related to substance abuse.
Another off-label use of trazodone is in the treatment of anxiety disorders (Bossini
et al. 2015; Charney et al. 1986; Rickels et al. 1993). Low-dosage trazodone has been
compared with the TCAs and benzodiazepines in the treatment of generalized anxiety
disorder. Small, mostly open-label studies have suggested benefit for the treatment of
anxiety in patients with MDD, panic disorder, and phobic disorders. Trazodone has
more recently found a place in veterinary medicine in the management of anxiety in
pets (Gruen et al. 2014; Orlando et al. 2016).
The primary drug interactions of trazodone are pharmacodynamic. Its sedating effects can be exacerbated by coadministration of other sedating CNS depressants, such
as benzodiazepines. Likewise, its α-adrenergic properties can exacerbate hypotension
when it is coadministered with antihypertensives. When combined with anticoagu-
and 5-HT2C antagonist (Haria et al. 1994). The
2A
-
371 Other Antidepressants: Bupropion, Mirtazapine, and Trazodone
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lants such as warfarin, trazodone can increase bleeding times. Its use is generally contraindicated in combination with MAOIs because of the risk of serotonin syndrome.
Trazodone is a CYP3A4 substrate and so can interact with inducers and inhibitors
of this isoenzyme (Haria et al. 1994). Thus, coadministration with CYP3A4 inhibitors
such as indinavir or ketoconazole may increase trazodone blood levels and increase
associated side effects. On the other hand, coadministration of trazodone with
CYP3A4 inducers such as rifampin, carbamazepine, or phenytoin may render it less
effective and require higher dosages. In turn, trazodone can increase the levels of phe
nytoin or digoxin, leading to toxicity associated with these drugs.
One of the metabolites of trazodone is meta-chlorophenylpiperazine, which is a hallucinogen and CYP2D6 substrate. Potent inhibitors of CYP2D6 such as fluoxetine and
paroxetine have very rarely been associated with an increase in agitation, dysphoria,
and hallucinations when combined with trazodone. The most common side effect of
trazodone relative to placebo is sedation and somnolence (PDR Staff 2017). In clinical
trials of trazodone, up to 40% of patients reported sedation or drowsiness, a rate that
was two to four times the rate reported in the patients given placebo. As a result, most
patients take trazodone primarily at night, although dosages greater than 100 mg/
day are usually given in divided doses. Although sedation is the most commonly re
ported side effect, nausea was one of the most common reasons patients discontinued
the drug in clinical trials. About 10% of patients reported nausea or vomiting in inpa
tient clinical trials with trazodone, compared with approximately 1% of placebotreated patients. Among its more dangerous side effects, particularly in the elderly, is
orthostatic hypotension; although the rate of hypotension is less than that seen with
TCAs, trazodone’s α
-adrenergic receptor antagonism effect increases the risk of falls
1
and syncope in older patients. The hypotension is dose related, and the risk is greater
at higher dosages than at lower ones.
Trazodone, like mirtazapine and bupropion, is associated with lower rates of sexual dysfunction than most antidepressants (Clayton et al. 2014). That said, it does
carry a risk of priapism that is not typical of other antidepressants. Priapism is medi
ated by the α
jection of an α
-blocking properties of trazodone and is treated either by the direct in-
1
agonist such as phenylephrine or, in some cases, by removal of excess
1
blood in the penis via needle aspiration or surgery (Saenz de Tejada et al. 1991). The
incidence of priapism is about 1/6,000, and the risk is higher among young males
than older patients.
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-
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References
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mer disease patients: a randomized, double-blind, and placebo-controlled study. Am J
Geriatr Psychiatry 22(12):1565–1574, 2014 24495406
Chang F-L, Ho S-T, Sheen MJ: Efficacy of mirtazapine in preventing intrathecal morphine-
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