Pharmacological Treatments

The mechanism of action of the drugs effective in treating OCD (clomipramine, a non-selective serotonin reuptake inhibitor, and the selective serotonin reuptake inhibitors [SSRIs]: citalopram, fluoxetine, fluvoxamine, sertraline and paroxetine) has given rise to the hypothesis that deficient serotonin function is a key element in the pathophysiology of OCD. These drugs block serotonin reuptake by the pre-synaptic neuron, thereby increasing serotonin availability at post-synaptic receptors. The serotonin hypothesis is also supported by the observation that m-CPP (a metabolite of trazodone), which is a partial agonist at serotonin receptor types 1A, 1D and 2C, exacerbates OCD.

About 40% to 60% of patients will respond to clomipramine or to any particular SSRI, and one cannot predict which patient will respond to which drug. A trial of 10-12 weeks at the maximum comfortably tolerated dose is usually necessary to determine whether a given drug is producing a clinically meaningful response. Direct, controlled comparison studies have found fluvoxamine, paroxetine and sertraline equal in efficacy to clomipramine, the first drug that was demonstrated to be effective in treating OCD. Our clinical practice is often to push the patient in weekly increments to the maximum easily tolerated SSRI (or clomipramine) dose, since it is not possible to predict the dose that will prove effective for an individual patient. For fluvoxamine, for example, we may start the patient at 25 or 50 mg/day and increases the dose every 5 to 7 days by 50 mg/day to a maximum daily dose of 300 mg/day if possible. 

Unpleasant side effects such as nausea, sexual dysfunction, sedation and weight gain can lead patients to discontinue clomipramine or SSRIs. Rare reports of akathisia, bleeding, easy bruising and suicidality exist. In the case of sexual side effects, anorgasmia or reduced libido may respond to bupropion 75-150 mg/day, buspirone 15-60 mg, amantadine 100-400 mg/day, methylphenidate 10-20 mg/day, dexedrine 5-10 mg/day or yohimbine 5.4-16.2 mg. Additional drugs that may help include sildenafil, mirtazapine and nefazodone. Queasiness is usually transient and can be minimized by lowering the dose and titrating up slowly. 

Over 10-12 weeks, symptoms decrease by about 40% to 50% or more in about 60% of patients. Disappearance of all symptoms rarely occurs. Benefit is usually noticeable after 6 weeks, but may take 8 weeks to begin. Non-responders to one SSRI may respond to another or to behavior therapy. Partial responders may benefit further from potentiating (augmenting) drugs or from adding behavior therapy (exposure and response prevention, or cognitive approaches). 

Numerous augmenting medications exist that have some research backing. While detailed information on how they are used is beyond the scope of this overview, they include memantine, risperidone, aripiprazole, N-acetyl cysteine, ondansetron, topiramate, lamotrigine, low-dose clomipramine (for patients on an SSRI), stimulants and, for the most refractory case, ketamine and morphine. 

Some patients may need to stay on medications indefinitely, since the available data suggest that patients' symptoms will return within one to two months after medications are stopped, even after two years of successful pharmacotherapy. A recent study suggests that 20% of patients who discontinue a successful drug will not respond when the drug is restarted. Available data suggest, but do not prove, that providing behavior therapy while the patient is taking medication may delay or prevent relapse when medication is discontinued. 

An exciting new chapter in the treatment of OCD involves interventional and neuromodulation approaches. Collectively, they can be seen to target the hyperactive cortico-striato-thalamo-cortical “loop" implicated in OCD. “Deep” transcranial magnetic stimulation is considered comparatively safe and may be particularly suited for patients who have difficulty tolerating medications. Other interventions, such as deep brain stimulation and psychosurgery via gamma knife or focused ultrasound ablation, are reserved for treatment-refractory cases.