The University of Florida
Obsessive-Compulsive Disorder Program
Medication Treatment
Before the late 1960's, OCD was generally viewed as unresponsive to a range of conventional therapies. Traditional talk therapy based on psychoanalytic principles was rarely successful in reducing the severity of obsessions or compulsions. Understanding and working through the symbolic meaning of obsessions may have enhanced a patient's understanding of the workings of his or her mind, but it proved insufficient in turning the tide of obsessive-compulsive behavior. The success rate with a range of different medications was just as disappointing.
Two developments mark the beginning of the modern era of the treatment of OCD. First, the British psychologist Victor Meyer reported in 1966 that two cases of OCD had responded to a behavior therapy technique later referred to as exposure and response prevention. Behavior therapy attempts to modify maladaptive behaviors by employing strategies that focus on the here-and-now. Second, several European psychiatrists reported in the late 1960's and early 1970's that a medication called clomipramine was effective in a series of cases of OCD. In a number of subsequent studies conducted around the globe, behavior therapy and clomipramine have each been established as effective treatments for OCD. The most broadly effective treatment for OCD appears to be a combination of clomipramine (or medications like it) and behavior therapy.
The only medications that have been consistently shown to be effective in treating OCD are antidepressants that interact with the brain chemical serotonin. Serotonin is one of the brain's many chemical messengers or neurotransmitters that allow one nerve cell (called a neuron) to communicate with another neuron. Instead of being joined directly together, most neurons are separated from each other by a narrow fluid-filled gap called the synapse. In order for an electrical signal to pass from one neuron to the next, neurotransmitter is released into the synapse where it floats freely across to the adjoining neuron. There it encounters a specialized part of the neuron called the receptor. The receptor is like a lock and the neurotransmitter the key. With the key in the lock, an electrical signal is triggered and passes along the receiving neuron to convey information elsewhere in the brain. In addition to interacting with the adjoining neuron, released serotonin is actively taken back up into the neuron from which it was released. This serotonin reuptake pump acts to recycle serotonin, assisting in re-claiming it for later release. It also may serve to reduce the amount of "noise" that would be generated if too much serotonin lingered in the synapse after each nerve firing.
The modern era in the pharmacotherapy of OCD began in the late 1960's with the observation that clomipramine (Anafranil®) and not other tricyclic antidepressants such as imipramine (Tofranil®) was effective in OCD. Clomipramine is the most thoroughly studied drug in OCD and was the first to receive FDA approval for this indication. Clomipramine has a number of different chemical properties, including the ability to latch on to the serotonin reuptake pump and prevent the movement of serotonin into its home neuron. Medications, like clomipramine, that block the serotonin pump are referred to as serotonin reuptake inhibitors or SRIs. In addition to clomipramine, several selective SRIs have been shown effective in treating OCD, including fluvoxamine (Luvox®), fluoxetine (Prozac®), sertraline (Zoloft®), and paroxetine (Paxil®). Some evidence suggests the selective SRI citalopram (Celexa®) may also be effective for OCD, even though it does not have FDA approval for this indication.
In a series of different studies, researchers have shown that SRIs are more effective in treating OCD than other antidepressants that do not interact with the serotonin pump. Thus, all SRIs can treat depression, but not all antidepressants can treat OCD. For example, desipramine, which is not an SRI, is an effective antidepressant but is ineffective in treating obsessive-compulsive symptoms. This specificity of response lends weight to the widely-held opinion that OCD involves a biochemical imbalance.
SRIs take time to work. Daily treatment for 8 - 12 weeks may be required before the symptoms of OCD begin to recede. Once improvement occurs, the medication is usually continued for at least another 6 - 12 months. Some patients can be successfully tapered off medication, but the majority seems to relapse after complete discontinuation of medication. Adding behavior therapy may reduce the rate of relapse off medication. Nearly two-thirds of patients with OCD experience significant symptom relief on SRIs. Among those that do improve, the degree of change is meaningful, but it is rarely complete. A person with OCD who has had a good response to an SRI might report that the time occupied by obsessions and compulsion is cut from 6 to 2 hours a day. This may allow that individual to return to work or school and resume a relatively normal and fulfilling life. Interestingly, how long someone has had OCD does not predict how well they will respond to SRI treatment. Marked improvement can be observed even after 35 years of continuous obsessive-compulsive symptoms.
SRIs are not without side effects. Nausea, tremors, diarrhea, insomnia, and daytime drowsiness are some of the common side effects of the SRIs. Clomipramine may produce additional unpleasant symptoms, including dry mouth, constipation, and urinary retention. Impotence and delayed or failed orgasm occurs with clomipramine. Many patients complain of fatigue and weight gain. It also has risks associated with it, including possible adverse affects on heart rhythm, seizures, and death with overdose. The risk of seizures increases significantly at doses over 250 mg daily. Some patients will tolerate one SRI better than they will tolerate another, but for the most part the selective SRIs listed above are better tolerated than clomipramine. With help from their doctor, most patients can find a dosage of medication that relieves symptoms while keeping side effects to a tolerable level.
Selecting a Specific Medication Strategy
Among the classes of medications, the serotonin reuptake inhibitors (SRIs) are by far the most effective for OCD and the experts recommend all five SRIs as first line treatments for OCD (clomipramine, fluoxetine, fluvoxamine, paroxetine, and sertraline). If the patient does not respond to the average dose of an SRI, the experts recommend gradually increasing the dose to its maximum within 4–8 weeks from the start of treatment. When a patient is having a partial response to an average dose of an SRI, the experts suggest gradually increasing the dose to its maximum within 5–9 weeks from the start of treatment. They consider 8–13 weeks an adequate medication trial before changing medication or augmenting with another agent.
When increasing the dose to the maximum, it is generally wise to wait 2–4 weeks between dose increases to allow sufficient time to establish a dose-response relationship. A few patients who show a partial response to medication and few side effects may benefit from doses substantially higher than those listed as the conventional maximum. The dose of medication for such patients should not be increased to high levels until at least 12 weeks of treatment have elapsed.
The experts recommend switching to another SRI if there is no response after 4–6 weeks at a maximum dose. Other treatments, including venlafaxine, MAOIs, and clonazepam, are considered third line and may be worth a try when the SRIs themselves have not proven helpful.
Unfortunately, Not Everyone Improves With Initial Treatment.
Despite recent advances in behavior and medication treatment, about one-third of people with OCD fail to experience improvement.
Experts recommend adding an SRI when patients have not responded well to CBT alone. When patients have not done well with medication management alone, experts recommend either adding CBT or switching to another SRI. Thus, combined CBT and medication is the experts’ preference for most patients who have not responded to an initial trial of either CBT or medication alone. In patients who have shown no response to combined treatment, the experts recommend switching SRIs and continuing CBT. In patients with a partial response to combination therapy, they recommend switching SRIs, providing more CBT, and possibly augmenting with another medication.
Strategies for the Treatment-Refractory Patient
The experts have somewhat less agreement about what to do next in managing treatment-refractory patients (those who fail to respond to well-delivered sequential SRI trials combined with expert CBT). They recommend adding an augmenting medication, especially if the patient exhibits associated features (e.g., tics or a comorbid anxiety disorder) that might predict a positive response to augmentation. Second line recommendations are to try a new CBT setting, technique, or intensity, or to switch to another SRI or an MAOI. Finally, in patients with extremely severe and nonremitting OCD, IV clomipramine, neurosurgery, (internal capsulotomy) or ECT (if the patient is also depressed) may sometimes be considered.
There are a variety of augmentation strategies that can be tried in OCD, including clomipramine, clonazepam, conventional neuroleptics, buspirone, risperidone, and a second SSRI added to the first one. The experts suggest tailoring the choice of augmentation medications to the individual clinical presentation. Clomipramine may be useful in boosting the response of a patient treated with an SSRI who is not having an adequate response. Neuroleptics may be helpful for patients who are not having an adequate response to an SRI and who have a comorbid tic disorder; OCD symptoms such as compulsive touching that resemble tics; or comorbid schizotypy. Clonazepam may be a helpful augmentation agent for patients with a comorbid anxiety disorder.
Treatment Strategies for the Maintenance Phase
Once patients have responded to the acute phase of treatment for OCD, it is important to consolidate treatment gains during the maintenance phase. The experts recommend monthly follow-up visits for at least 3–6 months and consider rapid discontinuation of medications unacceptable. Booster CBT sessions may help reduce the risk of relapse when medication is withdrawn. The experts recommend considering long-term or lifelong prophylactic maintenance medication after two to four severe relapses or three to four mild to moderate relapses.
The experts’ replies reflect a tendency to recommend continuing medication for longer periods in patients who are not receiving CBT, probably reflecting the higher probability of relapse in patients withdrawn from medication who have not also received CBT.
When patients are stable but still clinically symptomatic, they may be seen for medication maintenance or CBT booster sessions every 3 months, while patients in remission are seen yearly. Because, OCD is a lifetime waxing and waning condition, most OCD experts never end treatment, but leave the option open to return if OCD recurs.
Relapse prevention, including generalization training and booster sessions, especially when withdrawing medication, may increase the durability of CBT.
