Evidence-Based Reviews

Treating OCD in patients with psychiatric comorbidity

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High dosages of SRIs—selective serotonin reuptake inhibitors or the tricyclic antidepressant clomipramine—are first-line OCD medications (Table 3). Double-blind clinical trials have found clomipramine, fluoxetine, sertraline, paroxetine, fluvoxamine, and citalopram more effective than placebo, and the first five of these drugs are FDA-approved for treating adult OCD.

Table 3

Serotonin reuptake inhibitors indicated for treating OCD*

DrugStarting dosageTarget dosage (adults)
Clomipramine25 mg/d150 to 200 mg/d
Fluoxetine20 mg/d60 to 80 mg/d
Fluvoxamine50 mg/d150 to 300 mg/d
Paroxetine20 mg/d40 to 60 mg/d
Sertraline50 mg/d150 to 200 mg/d
* 10- to 12-week medication trials at target doses; sequential trials may be required to achieve treatment response.
Side effects. SRI dosages required to treat OCD may lead to intolerable side effects, including sedation, insomnia, GI side effects, and sexual dysfunction. Clomipramine is rarely used as a first-line agent because of its anticholinergic side effects.

Nonresponse. Patients typically require at least 10 to 12 weeks of treatment at target dosages. Sequential medication trials may be needed to achieve a response. Complete remission is rare, and relapse rates are high when medication is discontinued.22

The up to 40% of patients who do not respond to SRI therapy require alternate strategies:

  • Augmenting SRI therapy with a low-dose atypical antipsychotic such as risperidone, 1 to 2 mg bid, or olanzapine, 5 to 10 mg/d, may be effective, even in patients without a comorbid psychotic or tic disorder.23,24 It is worth noting that trials using atypicals as adjunctive therapy for OCD have been brief (12 weeks), and long-term use of these medications carries a risk of metabolic side effects such as weight gain, diabetes, and hyperlipidemia.
  • The serotonin-norepinephrine reuptake inhibitor venlafaxine, 225 mg/d or higher, showed efficacy in a naturalistic study of patients who did not respond to SRIs.25
  • Augmentation with pindolol, lithium, buspirone, trazodone, tryptophan, or thyroid hormone has shown mixed results.24


Acute risk? Conditions that endanger the patient take precedence over OCD treatment. Suicidal risk and self-mutilating behaviors, for instance, must be addressed before a patient can engage in ERP therapy. Active psychosis also would exclude ERP and may be best handled by augmenting SRI therapy with an antipsychotic.17

Interfere with CBT? Exposure therapy can exacerbate symptoms in patients who self-medicate their anxiety with alcohol or other substances. In turn, alcohol or other substance abuse may interfere with habituation by ameliorating the anxiety necessary for effective exposure therapy. Thus, we recommend delaying OCD behavioral treatment until you treat or stabilize these conditions.

Many OCD patients report comorbid depression, which may be secondary to their OCD symptoms and may spontaneously decrease with successful OCD treatment. Patients with mild to moderate depression can usually engage in and benefit from ERP without depressionspecific interventions.

Patients with comorbid depression may not respond to OCD interventions as well as nondepressed OCD patients do.26 For concurrent OCD and major depression, expert consensus guidelines suggest combining CBT with an SRI.17

Less is known about how other comorbidities affect OCD treatment. In one study, patients with comorbid OCD and posttraumatic stress disorder (PTSD) responded poorly to ERP. Exposure therapy reduced OCD symptoms but increased PTSD symptoms in some patients.27 Some Axis II disorders—such as schizotypal, avoidant, paranoid, and borderline personality disorder—have also been found to predict poorer outcome in patients treated with clomipramine.3

Concurrent treatment? In some concomitant conditions, such as PTSD with OCD, preliminary evidence suggests that treatment can or should be simultaneous rather than sequential.27 Likewise, CBT can be used to treat OCD concurrent with other anxiety disorders with only slight modifications, such as:

  • constructing exposures for social anxiety disorder patients that, at least initially, minimize extraneous social contact and evaluative fears
  • instructing panic disorder patients in anxiety management skills so that exposures do not trigger anxiety attacks and reinforce their fears.
The same medications are appropriate for some overlapping conditions such as depression and anxiety disorders, which simplifies simultaneous drug therapy. Treatment is more complicated in OCD patients with bipolar disorder, however, as the antidepressants used to treat OCD can induce mania or hypomania and worsen the mood disorder.28 In these patients, stabilize mood before starting an antidepressant.

Related resources

  • Jenike MA, Baer L, Minichiello WE (eds). Obsessive-compulsive disorders: practical management (3rd ed). New York: Mosby, 1998.
  • Clark DA. Cognitive-behavioral therapy for OCD. New York: Guilford Press, 2003.
  • Obsessive-Compulsive Foundation. www.ocfoundation.org.
Drug brand names
  • Buspirone • BuSpar
  • Citalopram • Celexa
  • Clomipramine • Anafranil
  • Fluoxetine • Prozac
  • Fluvoxamine • Luvox
  • Olanzapine • Zyprexa
  • Paroxetine • Paxil
  • Risperidone • Risperdal
  • Sertraline • Zoloft
  • Trazodone • Desyrel
  • Venlafaxine • Effexor

The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.


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