Drug Information Rounds

Use of Risperidone as Augmentation Treatment for Major

Depressive Disorder

Ryan K Owenby, Lindsey T Brown, and Jamie N Brown

Request
Is risperidone a safe and effective aug-
mentation treatment option for major de-
pressive disorder (MDD) in patients who
fail to achieve adequate response to an-
tidepressant monotherapy?
Response
BACKGROUND
MDD is a common psychiatric disor-
der that causes alterations in mood and
thinking. This has been shown to affect
physical health and overall well-being, as
well as impact work and personal rela-
tionships.1 The World Health Organiza-
tion currently ranks depression as the
leading cause of disability and as a large
OBJECTIVE: To review the efficacy and safety of risperidone for augmentation
treatment in patients with major depressive disorder who fail to achieve adequate
response to antidepressant monotherapy.
DATA SOURCES: A search of MEDLINE (1966-August 2010) and EMBASE (1980-
August 2010) was conducted, using the terms risperidone and major depressive
disorder. In addition, a manual search of the references cited in each publication
identified from the database search was conducted to identify relevant articles.
STUDY SELECTION AND DATA EXTRACTION: All English-language, peer-reviewed
publications identified from the data sources were evaluated. Four clinical trials
and 1 subanalysis of a clinical trial were included for analysis.
DATA SYNTHESIS: Risperidone is an atypical antipsychotic that displays anti-
depressant properties due to its activity at various serotonergic and dopaminergic
receptors. Studies have demonstrated that risperidone augmentation may be
effective and safe when used at low doses. Although several of the studies
identified had limited sample sizes, all studies demonstrated improvement on
various standardized depressive symptom assessment scales. Study durations
ranged from 4 to 24 weeks, with doses ranging from 0.25 to 2 mg/day. The most
common adverse effects associated with risperidone therapy were headache, dry
mouth, and increased appetite.
CONCLUSIONS: Clinical evidence suggests that the use of risperidone as

contributor to global burden of disease.
The estimated lifetime and 12-month risk
of experiencing MDD is 13.23% and
5.28%, respectively, and the average age
at onset is approximately 30.4 years.
MDD is twice as common in females as
in males, and it is often associated with
2 adjunctive therapy for treatment-resistant depression may improve rates of
response and remission, but long-term effectiveness and safety cannot be
determined at this time. Therefore, an adequate trial of first-line agents from
different classes and/or a combination of agents from different classes would be
recommended prior to initiation of risperidone. If the decision is made to start
risperidone, health-care providers should ensure that patients are educated
regarding the potential benefits and adverse effects before initiating risperidone.
KEY WORDS: augmentation, major depressive disorder, risperidone.

various comorbidities including anxiety Ann Pharmacother 2011;45:95-100.

and personality disorders.3 The exact Published Online, 28 Dec 2010, theannals.com, DOI 10.1345/aph.1P397
cause of MDD is unknown; however,
proposed mechanisms suggest that multi-
ple contributing factors may play a role in the disorder. neurotransmitters, including serotonin (5-HT), norepineph-
Suggested hypotheses include a deficiency in monoamine rine, and dopamine, as well as a dysregulation of these
neurotransmitter systems.
Achieving an adequate response and remission is chal-
Author information provided at end of text. lenging in the treatment of MDD. The STAR*D trial evalu-

theannals.com The Annals of Pharmacotherapy n 2011 January, Volume 45 n 95

Downloaded from aop.sagepub.com at YildizTeknik Univ on January 5, 2015
RK Owenby et al.
ated response and remission rates in patients with nonpsy-
chotic MDD who were adequately treated with citalopram.4
A response, defined as a 50% reduction in baseline symp-
toms, was seen in only half the patients treated with citalo-
pram, and only one third of the population achieved remis-
sion. The STAR*D trial clearly demonstrated the need for
alternative pharmacologic options in the management of
MDD to achieve greater response and remission rates and
decrease the risk of recurrence. Another trial, the Texas
Medication Algorithm Project (T-MAP), utilized an algo-
rithm-based disease management program for the treat-
ment of multiple mental illnesses including nonpsychotic
MDD.5 Similar to STAR*D, the T-MAP trial demonstrated
that even among treatment responders substantial symp-
toms persisted, indicating that many patients may require
additional therapies in order to control and treat MDD.
If goals of therapy are not achieved with antidepressant
monotherapy, one potential option is augmentation therapy
by adding an additional nonantidepressant pharmacologic
agent.6 Risperidone, an atypical antipsychotic, exhibits an-
tidepressant properties due to its antagonistic activity at the
dopamine type 2 (D2) and serotonin type 2 (5-HT2) recep-
tors and has potent agonistic activity at the 5-HT1D recep-
tor.7 Currently, risperidone has Food and Drug Administra-
tion (FDA)-approved labeling for the treatment of
schizophrenia, bipolar I disorder, and the management of
irritability in pediatric patients with autistic disorder. How-
ever, in the clinical setting, risperidone is used to treat and
manage several additional conditions, including acute agi-
tation, dementia, psychotic disorders, and refractory de-
pression. Risperidone is typically dosed at 1-3 mg orally 1-
2 times daily. Dose titration is necessary and is recom-
mended at 1 mg/day.8
Although risperidone appears to be well tolerated and
less likely to cause extrapyramidal adverse effects com-
pared to typical antipsychotics, it has been associated with
the development of metabolic disorders including obesity,
dyslipidemia, and diabetes.9,10 In addition, recent evidence
suggests that atypical antipsychotics may increase the risk
of sudden cardiac death in a dose-related fashion.11 It also
may have the potential for other serious adverse effects
such as serotonin syndrome and neuroleptic malignant
syndrome.8 The objective of this literature review is to de-
termine the efficacy and safety of risperidone augmenta-
tion for the treatment of MDD.
DATA SOURCES
A comprehensive search was conducted using MEDLINE
(1966-August 2010) and EMBASE (1980-August 2010)
with search terms of risperidone and major depressive dis-
order, limiting results to humans and the English language.
In addition, a manual search of the references cited in each
publication identified from the database search was con-
96 n The Annals of Pharmacotherapy n 2011 January, Volume 45
Downloaded from aop.sagepub.com at YildizTeknik Univ on January 5, 2015
ducted to further identify relevant articles. Studies were in-
cluded if they evaluated the use of risperidone as augmen-
tation therapy in treatment-resistant or difficult-to-treat de-
pression in patients currently on an antidepressant medica-
tion. Four clinical trials and a subanalysis of 1 of the
clinical trials are included in this review (Table 1).12-16
EFFICACY
Clinical Studies
Anecdotal case series regarding the efficacy of risperi-
done for treatment-resistant depression were first described
by Ostroff and Nelson when reporting 8 cases in which
MDD was effectively treated with risperidone.17 Viner et
al. further described the successful treatment of 5 females
with suicidal ideation refractory to conventional thera-
pies.18 Since those reports, multiple clinical trials have
evaluated the use of risperidone as augmentation therapy.
One trial evaluated the efficacy of risperidone augmen-
tation in an open-label phase and then assessed the time to
relapse in a 24-week double-blind continuation phase for
patients achieving remission with risperidone augmenta-
tion.12 Patients were eligible to receive citalopram
monotherapy if their baseline Hamilton Rating Scale for
Depression (HAM-D) total score was ≥20. Those demon-
strating less than a 50% reduction in score after 4-6 weeks
of treatment were considered nonresponders. A total of
386 patients entered the open-label augmentation phase
and received risperidone at a mean dose of 1.1 ± 0.6
mg/day, in addition to their current dose of citalopram. The
Montgomery-Åsberg Depression Rating Scale (MADRS)
scores used to assess severity of depressive symptoms
were significantly reduced from baseline in patients receiv-
ing risperidone augmentation.12
In the same trial, 241 patients who achieved resolution
of symptoms, defined as a HAM-D score ≤7 or a Clinical
Global Impressions-Severity (CGI-S) score of 1 or 2, were
then randomized to receive either placebo or continuation
of risperidone in addition to citalopram.12 The average dai-
ly dose of risperidone during the double-blind continuation
phase was 1.2 ± 0.6 mg. Relapse was determined by the
presence of 1 or more of the following 4 criteria: CGI-S
score of 6 or 7, HAM-D score ≥16, discontinuation due to
lack of therapeutic effect, or deliberate self injury or suici-
dal intent. Continuation of risperidone augmentation did
not significantly increase the median time to relapse com-
pared to the placebo group despite a trend toward improve-
ment in time to relapse with low-dose risperidone.12
Later, Alexopoulos et al.13 conducted a subset analysis
on a group of patients from the Rapaport et al.12 study to
determine whether risperidone augmentation delays the
time to relapse in older patients with depression. Patients
between 55 and 85 years of age were evaluated to deter-
theannals.com
 Risperidone Augmentation for Major Depressive Disorder

mine whether the benefits of continuing treatment with
risperidone outweighed the risk, since this population is at
a greater risk of experiencing adverse effects, such as tar-
dive dyskinesia and death.13 Ninety-three patients received
risperidone augmentation, 63 of whom met remission cri-
teria and were eligible for the 24-week double-blind main-
tenance phase. The mean modal doses of risperidone were
0.7 ± 0.3 and 0.8 ± 0.3 mg/day during the open-label aug-
mentation phase and double-blind continuation phase, re-
spectively. Of the 32 patients in the risperidone group, 18
(56%) experienced relapse, compared to 20 (65%) of the
31 patients in the placebo group. Although there was a
longer time to relapse in the risperidone group, this trial
was not adequately powered to detect significant differ-
ences between groups. The results of this study suggest
that continuing low-dose risperidone may have a potential
role in stabilizing remission in older patients; however, this
study is limited by the 56% and 65% relapse rates in the
risperidone and placebo groups, respectively.13
Another double-blind, placebo-controlled trial evaluated
risperidone augmentation after a failure to respond to a 4-
week prospective run-in phase with a standard antidepres-
sant.14 Although various antidepressants were used during
the run-in phase, about 60% of patients were receiving a
selective serotonin reuptake inhibitor (SSRI). Upon com-
pletion of the run-in phase, 274 patients were eligible to
enter the double-blind phase. Patients were randomized to
receive either risperidone titrated up to 1 mg/day or place-
bo for 6 weeks in combination with their current antide-
pressant. If the treatment response was determined to be
insufficient, then an increase in dose to 2 mg/day was an
option. The primary endpoint was the rate of response and
remission based on changes in HAM-D scores from base-
line to study end. Response and remission were defined as
a ≥50% reduction in HAM-D score from baseline and a
HAM-D score ≤7, respectively. Primary endpoints were
assessed at weeks 4 and 6, and significant differences be-
tween treatment groups were demonstrated at each time
point. Significant improvements were noted in the risperi-
done treatment group with various other patient- and clini-
cian-rated measures regarding global impression severity,
quality of life, and disability. Again, improvements with
risperidone augmentation were evident as early as week 1
of therapy. The use of various antidepressants in the run-in
phase may be considered a strength of this study, because a
wide variety of agents are also used in clinical practice.
However, it is difficult to draw conclusions about specific
antidepressant-risperidone combinations for treatment of
MDD based on this study. The results of this trial support
the findings from previous studies demonstrating a rapid
response of symptom improvement with risperidone aug-
mentation.14

Table 1. Clinical Studies of Risperidone Augmentation

Baseline
Reference Design Pts., N Antidepressant(s) Outcomes Results
12
Rapaport (2006) OL Augmentation Citalopram MADRS score MADRS score reduced from 27.7 ± 7.2 to 13.2 ± 10.1
phase: 386 (p < 0.001)
DB, PC Continuation Citalopram Median time Median time to relapse: risperidone 102 days; placebo 85
phase: 241 to relapse days (p = 0.52)
Mahmoud (2007)14 DB, PC 274 SSRIs, SNRIs, HAM-D score Week 4:
other (trazodone, remission: risperidone 13.6% vs placebo 6.0% (p = 0.041)
bupropion) response: risperidone 35.6% vs placebo 18.8% (p = 0.002)
Week 6:
remission: risperidone 24.5% vs placebo 10.7% (p = 0.004)
response: risperidone 46.2% vs placebo 29.5% (p = 0.004)
Reeves (2008)15 DB, PC 24 SSRIs, SNRIs, BSSI Risperidone group: 23.92 ± 9.29 to 14.93a; placebo group:
TCAs, other 24.91 ± 9.21 to 19.29 ± 10.77 (p = 0.0611)
(nefazodone,
bupropion)
Alexopoulos (2008)13 OL Augmentation Citalopram MADRS score Reduced 0.43 ± 0.31 points per day
phase: 93
DB, PC Continuation Citalopram Median time Median time to relapse: risperidone 105 days; placebo 57
phase: 63 to relapse days (p = 0.069)
Keitner (2009)16 DB, PC 97 SSRIs, SNRIs, MADRS Remissionb: risperidone 51.6% vs placebo 24.2% (p = 0.011);
other (bupropion, score response: risperidone 54.8% vs placebo 33.3% (p = 0.049)
trazodone,
nefazodone,
mirtazapine)

BSSI = Beck Scale for Suicide Ideation; DB = double-blind; HAM-D = Hamilton Rating Scale for Depression; MADRS = Montgomery-Åsberg De-
pression Rating Scale; OL = open-label; PC = placebo-controlled; SNRI = serotonin-norepinephrine reuptake inhibitor; SSRI = selective serotonin re-
uptake inhibitor; TCA = tricyclic antidepressant.
a
Calculation based on interpretation of study figure and estimation of reported percent reduction.
b
Remission defined as MADRS score ≤10.

theannals.com The Annals of Pharmacotherapy n 2011 January, Volume 45 n 97

Downloaded from aop.sagepub.com at YildizTeknik Univ on January 5, 2015
RK Owenby et al.
A double-blind, placebo-controlled, pilot study also
evaluated the effect of risperidone augmentation on suici-
dality in 24 patients whose symptoms were not adequately
controlled on antidepressant therapy.15 Patients were ran-
domized to receive risperidone or placebo in addition to
their current antidepressant. Risperidone was initiated at a
dose of 0.5 mg/day, allowing titration to a maximum of 2
mg/day or down to 0.25 mg/day based on clinical response
and reported adverse effects. The primary efficacy measure
was severity of suicidality, determined using the Beck
Scale for Suicide Ideation (BSSI). Additional rating scales,
including MADRS; Profile of Mood States; the Barratt Im-
pulsiveness Scale, Version 11; and the CGI-S, were used to
evaluate other core symptoms of depression, impulsivity,
and severity of clinical symptoms. Both groups demon-
strated a 22% reduction in BSSI scores after week 1 of
treatment, and an additional 20% reduction was seen in the
risperidone group by the end of week 8 of treatment. The
risperidone group demonstrated a significant reduction in
BSSI scores from baseline at each week of treatment (p <
0.005), and the overall reduction at the end of treatment
was significant (p = 0.0004). However, the reduction in
BSSI scores from baseline was not statistically significant
in the risperidone group when compared with the placebo
group (p = 0.0611). Significant improvements were also
observed in other core symptoms, including reductions in
total mood disturbance scores from baseline (p = 0.0005)
and significant differences in the patterns of impulsivity
between groups (p = 0.0154), with risperidone being asso-
ciated with lower impulsivity. This study demonstrates im-
provements with suicidal ideation and other core symp-
toms of MDD.15
Another randomized, placebo-controlled trial assessed
the efficacy of risperidone augmentation in patients who
failed to respond to or had a partial response to a 5-week
open-label trial of a single adequately dosed antidepres-
sant.16 The primary outcome measure was remission, de-
fined as a MADRS score ≤10. Ninety-seven patients were
eligible for entry into the augmentation phase, where pa-
tients were randomized in a 2:1 ratio to receive either
risperidone, initiated at 0.5 mg/day with titration to a maxi-
mum of 3 mg/day based on clinical response, or placebo
for 4 weeks. The average risperidone dose in this trial was
1.6 ± 0.73 mg/day. Results were based on a modified in-
tent-to-treat analysis (ITT). The modified ITT group in-
cluded all randomized patients who received at least 1 dose
of study medication. By the end of the 4-week treatment
phase, statistically significant improvements in the rate of
response and remission were observed in the risperidone
group compared to placebo. The short duration of this
study makes it difficult to assess the efficacy of long-term
risperidone augmentation in maintaining remission and
preventing relapse.16
98 n The Annals of Pharmacotherapy n 2011 January, Volume 45
Downloaded from aop.sagepub.com at YildizTeknik Univ on January 5, 2015
SAFETY
Although risperidone was administered for augmenta-
tion treatment at low doses and was generally well tolerat-
ed, the study durations were primarily short-term and do
not provide information related to its long-term effects.
The studies by Rapaport et al.12 and Mahmoud et al.14 as-
sessed the development of dyskinesia, dystonia, akathisia,
and parkinsonism with various rating scales, and no signif-
icant differences between risperidone and placebo in either
trial were identified. One to 2 patients experienced ex-
trapyramidal symptoms in both treatment groups in the tri-
al evaluating use in patients with suicidal ideations; how-
ever, the Abnormal Involuntary Movement Scale score
and Simpson-Angus Scale scores were low for these
events.12,15 Mahmoud et al. reported discontinuation rates
due to adverse events in the risperidone and placebo
groups at 5.8% and 2.3%, respectively; the specific causes
of discontinuation due to risperidone included somnolence,
malaise, weight gain, disturbance in attention, depression,
insomnia, and panic attack.14
The most commonly reported adverse events associated
with risperidone use included headache, dry mouth, in-
creased appetite, and weight gain.12-16 The incidence of
headache was reported between 8.7% and 11.5%, while
the incidence of dry mouth was reported as high as
30.4%.15 Weight gain, defined as ≥7% increase from base-
line, was reported at 8.3% and 2.6% in the risperidone and
placebo groups, respectively.12 The subanalysis of older pa-
tients receiving risperidone demonstrated a significant dif-
ference with regard to weight gain between the risperidone
and placebo groups. Patients in the risperidone group expe-
rienced a mean 1.95 ± 2.27 kg weight gain, compared to
0.14 ± 2.27 kg increase with placebo (p = 0.0002).13
A few studies demonstrated elevated prolactin levels in
patients receiving risperidone. Levels were significantly in-
creased in the risperidone group in the study by Rapaport
et al., with an average prolactin level of 35.4 ± 53.4 ng/mL
and 6.6 ± 21.0 ng/mL for the risperidone and placebo
groups, respectively (p < 0.001).12
Discussion
Studies have demonstrated a clear need for additional
treatment options in the management of MDD since fre-
quently, antidepressant monotherapy does not produce ade-
quate rates of response and/or remission.4,5 Several strategies
are available for patients who remain symptomatic despite an
adequate trial of an antidepressant. These options include
switching from one SSRI to another, adding an antidepres-
sant from a different class, or augmenting therapy with other
agents, such as atypical antipsychotics.19 Currently, the atypi-
cal antipsychotics aripiprazole and quetiapine have FDA-ap-
proved labeling for the adjunctive treatment of MDD. Remis-
theannals.com

sion rates of 25% and 30% and response rates of 33.7% and
>50% have been reported for aripiprazole and quetiapine, re-
spectively.20-22 However, what often limit the use of these
agents are their adverse effect profiles. The risk of weight
gain and metabolic disturbances appears to be less with ari-
piprazole compared to quetiapine and risperidone, but the in-
creased risk of diabetes is less clearly associated with queti-
apine and risperidone.23
The evaluation and determination of response and re-
mission can be challenging considering the subjectivity of
depressive symptoms. Consequently, numerous assessment
scales have been developed in an effort to improve the evalu-
ation of patients with depression. A variety of standardized
assessment scales, both clinician-rated and patient-rated,
were used in the studies identified in this review, and all dis-
played similar results. In 2 studies, patients treated with low-
dose risperidone experienced greater response and remission
rates compared to those receiving placebo.14,16 However,
Keitner et al.16 defined remission as a MADRS score <10,
which differs from the current gold standard for remission,
defined as a MADRS score <8. Risperidone also trended to-
ward a longer time to relapse when compared to placebo;
however, the difference between groups was not significant.
Augmentation with risperidone was also shown to decrease
suicidal ideations, a major concern with MDD.15 The consis-
tency of results despite utilization of different standardized
assessment scales serves to strengthen the conclusion that
low-dose risperidone may have a role in this patient popula-
tion. It also enhances generalizability, since clinicians may
employ multiple assessment scales when evaluating patients
clinically.
Overall, low-dose risperidone was well tolerated. De-
spite the reports of headache, dry mouth, and weight gain,
these adverse effects did not significantly affect discontinua-
tion rates.12,14,16 Perhaps the most concerning adverse effect
was the significant amount of weight gain observed in
risperidone-treated patients. This is a common adverse effect
associated with atypical antipsychotics and is a major con-
tributor to long-term metabolic disturbances. For this reason,
clinicians must be cautious when initiating risperidone in pa-
tients with a history of cardiovascular disease, diabetes, and
hyperlipidemia. There is also concern for development of
extrapyramidal symptoms; however, the studies in this re-
view demonstrated a very low incidence with risperidone
0.25-2 mg/day for up to 24 weeks.12-15 The risk of metabolic
disturbances or extrapyramidal symptoms with low doses of
risperidone taken for greater than 24 weeks cannot be deter-
mined by the studies in this review.
In spite of the evidence supporting the use of low-dose
risperidone for augmentation therapy, some questions still
remain. A majority of patients were receiving antidepres-
sant monotherapy with an SSRI and some studies enrolled
patients receiving a variety of antidepressant agents. Al-
though this may be more representative of the general pa-
theannals.com
Downloaded from aop.sagepub.com at YildizTeknik Univ on January 5, 2015
Risperidone Augmentation for Major Depressive Disorder
tient population, it hinders the ability to identify the most
effective risperidone-antidepressant combination. Also, be-
cause of the differences in dosing strategies and treatment
duration, specific conclusions on the appropriate doses and
duration cannot be made. Additional research is needed to
delineate the optimal dose, duration, and treatment strategy
for risperidone augmentation. Larger randomized, con-
trolled clinical trials are also needed to determine the true
effectiveness of low-dose risperidone augmentation in the
improvement of suicidal ideation.
Summary
SSRIs remain first-line treatment for patients with
MDD. Current evidence suggests that low-dose risperi-
done may improve rates of response and remission, but the
long-term effectiveness and safety of low-dose risperidone
augmentation cannot be determined at this time. Therefore,
before initiating risperidone augmentation in patients who
fail first-line treatment with an SSRI, consider a trial of a
different SSRI or switching to an agent from a different
class of antidepressants. If the decision is made to start
risperidone, health-care providers should ensure that pa-
tients are educated regarding the potential benefits and ad-
verse effects before initiating risperidone.
Ryan K Owenby PharmD, Pharmacy Practice Resident, Durham
VA Medical Center, Durham, NC
Lindsey T Brown PharmD, Community Pharmacist, Department
of Pharmacy Practice, College of Pharmacy and Health Sciences,
Campbell University, Buies Creek, NC
Jamie N Brown PharmD BCPS, Drug Information Specialist, Phar-
macy Service, Durham VA Medical Center
Correspondence: Dr. Owenby, owenbyr@gmail.com
Reprints/Online Access: www.theannals.com/cgi/reprint/aph.1P397
Conflict of interest: Authors reported none
References
1. Chisholm-Burns MA, Wells BG, Schwinghammer TL, et al. Pharma-
cotherapy principles & practice. New York, NY: The McGraw-Hill
Companies, Inc., 2008:569-82.
2. World Health Organization. www.who.int/mental_health/management/
depression/definition/en/ (accessed 2010 Apr 19).
3. Hasin DS, Goodwin RD, Stinson FS, Grant BF. Epidemiology of major
depressive disorder: results from the National Epidemiologic Survey on
Alcoholism and Related Conditions. Arch Gen Psychiatry 2005;62:
1097-106.
4. Trivedi MH, Rush AJ, Wisniewski SR, et al. Evaluation of outcomes with
citalopram for depression using measurement-based care in STAR*D: im-
plications for clinical practice. Am J Psychiatry 2006;163:28- 40.
5. Trivedi MH, Rush AJ, Crismon ML, et al. Clinical results for patients
with major depressive disorder in the Texas Medication Algorithm Pro-
ject. Arch Gen Psychiatry 2004;61:669-80.
6. Papakostas GI. Managing partial response or nonresponse: switching,
augmentation, and combination strategies for major depressive disorder.
J Clin Psychiatry 2009;70:16-25.
7. Richelson E, Souder T. Binding of antipsychotic drugs to human brain re-
ceptors: focus on newer generation compounds. Life Sci 2000;68:29-39.
8. Product information. Risperdal (risperidone). Titusville, NJ: Ortho-Mc-
Neil-Janssen Pharmaceuticals, June 2009.
The Annals of Pharmacotherapy n 2011 January, Volume 45 n 99
RK Owenby et al.
9. Barrett E, Blonde L, Clement S, et al. Consensus development conference
on antipsychotic drugs and obesity and diabetes. Diabetes Care 2004;27:
596-601.
10. Lebovitz HE. Metabolic consequences of atypical antipsychotic drugs.
Psychiatr Q 2003;74:277-90.
11. Ray WA, Chung CP, Murray KT, et al. Atypical antipsychotic drugs and
the risk of sudden cardiac death. N Engl J Med 2009;360:225-35.
12. Rapaport MH, Gharabawi GM, Canuso CM, et al. Effects of risperidone
augmentation in patients with treatment-resistant depression: results of
open-label treatment followed by double-blind continuation. Neuropsy-
chopharmacology 2006;31:2505-13.
13. Alexopoulos GS, Canuso CM, Gharabawi GM, et al. Placebo-controlled
study of relapse prevention with risperidone augmentation in older pa-
tients with resistant depression. Am J Geriatr Psychiatry 2008;16:21-30.
14. Mahmoud RA, Pandina GJ, Turkoz I, et al. Risperidone for treatment-re-
fractory major depressive disorder. Ann Intern Med 2007;147:593-602.
15. Reeves H, Batra S, May RS, et al. Efficacy of risperidone augmentation
to antidepressants in the management of suicidality in major depressive
disorder: a randomized, double-blind, placebo-controlled pilot study. J
Clin Psychiatry 2008;69:1228-36.
16. Keitner GI, Garlow SJ, Ryan CE, et al. A randomized, placebo-con-
trolled trial of risperidone augmentation for patients with difficult-to-treat
unipolar, non-psychotic major depression. J Psychiatr Res 2009;43:205-14.
17. Ostroff RB, Nelson JC. Risperidone augmentation of selective serotonin
reuptake inhibitors in major depression. J Clin Psychiatry 1999;60:256-9.
18. Viner MW, Chen Y, Bakshi I, Kamper P. Low-dose risperidone augmen-
tation of antidepressants in nonpsychotic depressive disorders with suicidal
ideation. J Clin Psychopharmacol 2003;23:104-6.
19. American Psychiatric Association. Practice guideline for the treatment of
patients with major depressive disorder (2nd edition). Am J Psychiatry
2000;157(4 suppl):1- 45.
20. Berman RM, Marcus RN, Swanink R, et al. The efficacy and safety of
aripiprazole as adjunctive therapy in major depressive disorder: a multi-
center, randomized, double-blind, placebo-controlled study. J Clin Psy-
chiatry 2007;68:843-53.
21. Cutler AJ, Montgomery SA, Feifel D, et al. Extended release quetiapine
fumarate monotherapy in major depressive disorder: a placebo- and du-
loxetine-controlled study. J Clin Psychiatry 2009;70:526-39.
22. Bauer M, Pretorius HW, Constant E, et al. Extended-release quetiapine
fumarate as adjunct to an antidepressant in patients with major depres-
sive disorder: results of a randomized, placebo-controlled, double-blind
study. J Clin Psychiatry 2009;70:540-9.
23. American Diabetes Association, American Psychiatric Association,
American Association of Clinical Endocrinologists, North American As-
sociation for the Study of Obesity. Consensus development conference
on antipsychotic drugs and obesity and diabetes. J Clin Psychiatry 2004;
65:267-72.
Uso de Risperidona como Tratamiento Concomitante para el
Trastorno Depresivo Mayor
RK Owenby, LT Brown, y JN Brown
Ann Pharmacother 2011;45:95-100.
EXTRACTO
OBJETIVO: Revisar la eficacia y seguridad de risperidona como
tratamiento concomitante en pacientes con trastorno depresivo mayor
(MDD) que no consiguen una adecuada respuesta con la monoterapia
antidepresiva.
FUENTES DE DATOS: Se realizó una búsqueda en MEDLINE (1966-agosto
2010) y (1980-agosto 2010) utilizando los términos “risperidona” y
“depresión mayor”. Además se llevó a cabo una búsqueda manual de las
referencias citadas en cada publicación identificada en la búsqueda
anterior, para localizar artículos relevantes.
100 n The Annals of Pharmacotherapy n 2011 January, Volume 45
Downloaded from aop.sagepub.com at YildizTeknik Univ on January 5, 2015
SELECCIÓN DE ESTUDIOS Y EXTRACCIÓN DE DATOS: Se evaluaron todos los
artículos revisados por pares publicados en inglés que se identificaron.
En el análisis se incluyeron 4 ensayos clínicos y 1 subanálisis de un
ensayo clínico.
SÍNTESIS DE LOS DATOS: Risperidona es un antipsicótico atípico que
muestra propiedades antidepresivas debido a su actividad en varios
receptores serotonérgicos y dopaminérgicos. Los estudios demuestran
que la asociación de risperidona al tratamiento antidepresivo puede ser
efectiva y segura cuando se emplea a bajas dosis. Aunque varios de los
estudios localizados incluían un número limitado de sujetos, todos ellos
demostraban mejoras en varias escalas estandarizadas de evaluación de
síntomas depresivos. La duración de los ensayos varió de 4 a 24
semanas con dosis de 0.25 a 2 mg/día. Los efectos adversos más
comunes asociados con risperidona fueron cefalea, sequedad de boca, e
incremento del apetito.
CONCLUSIONES: La evidencia clínica sugiere que el uso de risperidona
como terapia concomitante para el tratamiento de la depresión resistente
puede mejorar las tasas de respuesta y remisión, pero la eficacia a largo
plazo y la seguridad de este tratamiento no puede determinarse con los
datos disponibles. Por lo tanto, sería recomendable probar con fármacos
de primera elección de distintas clases y/o una combinación de los
mismos antes de recurrir a risperidona. Si se opta por utilizar
risperidona, antes de iniciar el tratamiento los profesionales sanitarios
deben asegurarse de que los pacientes conocen los beneficios potenciales
y las reacciones adversas del mismo.
Traducido por Juan del Arco
Addition de la Risperidone au Traitement de la Dépression Majeure
RK Owenby, LT Brown, et JN Brown
Ann Pharmacother 2011;45:95-100.
RÉSUMÉ
OBJECTIF: Revoir l’efficacité et l’innocuité de la risperidone lorsqu’ajouté
au traitement des patients souffrants de dépression majeure
insuffisamment soulagés par une monothérapie.
PROVENANCE DES DONNÉES: Une recherche des banques de données
MEDLINE (1966-août 2010) et EMBASE (1980-août 2010) a été
effectuée en utilisant les termes risperidone et dépression majeure. Cette
recherche a été complétée par une revue de la bibliographie des
publications identifiées.
SÉLECTION DES DONNÉES: Toutes les publications de langue anglaise
évaluées par des pairs ont été revues. Quatre études cliniques et 1
analyse complémentaire d’une de ces études ont été retenues pour cette
présente analyse.
RÉSUMÉ: La risperidone est un antipsychotique atypique qui possède des
propriétés antidépressives reliées à son action sur les récepteurs
sérotoninergiques et dopaminergiques. Les études ont démontré que
l’addition de faibles doses de risperidone peut être efficace et sécuritaire.
Bien que ces études portent principalement sur de petits échantillons de
patients, toutes ont démontré une amélioration des différentes échelles de
mesure de la dépression. La durée des études variaient de 4 à 24
semaines et les doses variaient de 0.25 à 2 mg/jour. Les effets
secondaires les plus fréquents incluaient les maux de tête, la sécheresse
de la bouche, et une amélioration de l’appétit.
CONCLUSION: Les évidences cliniques suggèrent que l’addition de
risperidone peut être utile dans le traitement de la dépression majeure
résistante à une monothérapie. Cependant son efficacité et son innocuité
à long-terme ne sont pas connues pour l’instant. Il serait donc préférable
de procéder à un essai adéquat des différents agents de première ligne
et/ou une combinaison de ces agents avant de penser à ajouter la
risperidone. Si la décision d’ajouter la risperidone est prise, les
professionnels de la santé devraient s’assurer que le patient est bien au
courant des bénéfices et risques potentiels d’une telle décision.
Traduit par Suzanne Laplante
theannals.com