Medication Treatment for Obsessive Compulsive Disorder
Medication is one of the first-line treatment options for OCD. In other words, it can be one of the first things you try on your OCD treatment journey, because it has been proven to be effective by decades of high quality research studies and clinical experience. Medication can be a standalone treatment and/or an adjunctive treatment - something that you take alongside doing exposure and response prevention (ERP) or another evidence-based treatment for OCD.
Q: What is the first-line medication treatment for OCD?
A: Selective Serotonin Reuptake Inhibitors (SSRIs) are the first-line medications for OCD. SSRIs and Clomipramine are the only medications found to be effective standalone treatments for OCD. The SSRIs include Citalopram (Celexa), Escitalopram (Lexapro), Fluoxetine (Prozac), Fluvoxamine (Luvox), Paroxetine (Paxil), and Sertraline (Zoloft).
Q: Is there a BEST SSRI for OCD?
A: No. All the SSRIs and Clomipramine appear to be equally effective for the treatment of OCD. Currently only Fluoxetine (Prozac), Sertraline (Zoloft), Fluvoxamine (Luvox), Paroxetine (Paxil), and Clomipramine (Anafranil) have U.S. Food and Drug Administration (FDA) approval for use in OCD. However, the use of Citalopram (Celexa) and Escitalopram (Lexapro) for OCD is also well supported with data and both medications appear to be just as effective as the other SSRIs. Escitalopram (Lexapro) is approved in Europe for treatment of OCD.
COMMON MYTHOLOGY: Despite the above, many psychiatrists and patients mistakenly believe that Fluvoxamine (Luvox) is the most effective SSRI for OCD. This myth began when Fluvoxamine (Luvox) became the first SSRI marketed and advertised as the preferred medication for OCD. Data, however, does not show any superiority of Fluvoxamine over any other SSRI for OCD. Head to head trials found that all the SSRIs had very similar efficacy for OCD.
Q: How do I choose between the different SSRIs?
Given that all SSRIs appear to be equally efficacious, the decision of which SSRI to try is based on multiple factors including: side-effect profiles, drug-drug interactions, an individual’s past response to an SSRI or history of a family member’s response to an SSRI, patient preference, and the half-life of each medication.
Q: How are SSRIs dosed when treating OCD?
A: Studies have shown that, on average, dosages of SSRIs up to two to three times higher than those typically used for depression and anxiety disorders yield the greatest benefits for OCD.
Q: How long should an SSRI trial be run before determining if it is effective or not?
A: Response to SSRIs takes longer in OCD than in depression or anxiety disorders. While benefits from SSRIs seem to begin soon after their initiation, the progress often occurs at a slow rate and therefore can take several weeks for it to be apparent to both patient and prescriber. An adequate trial of an SSRI for OCD requires eight to 12 weeks, with at least 6 of those weeks at the moderate to high doses required for effective treatment of OCD (for example, at least 40-60 mg/day of Fluoxetine or Paroxetine, or at least 200-300 mg/day of Fluvoxamine or Sertraline). However, it is important to point out that further improvement can continue well beyond the 12-week mark.
IMPORTANT TAKE HOME POINT: All too often SSRI trials for OCD are deemed failures despite the fact that the dosage was not high enough and/or the trial was not conducted for long enough to properly determine whether the particular SSRI could be effective for the patient. This is problematic since it often leads to either changing a patient’s medication prematurely to another medication with a more adverse side effect and/or augmenting the patient’s medication with additional medication(s) that could yield more adverse effects.
Q: How effective are SSRIs for OCD?
A: With any given trial of an SSRI, about 40-60% of patients with OCD will have a clinically significant improvement in OCD symptoms and overall functioning. For those who respond, the average degree of improvement is a 40-50% decrease in the severity of OCD symptoms.
Q: If an SSRI trial yields a satisfactory response, how long should one continue to treat?
A: OCD is a chronic condition, and, like most medications, SSRIs are helpful when you take them but do not appear to have continued positive effects years after treatment is stopped. The relapse rate of those patients who discontinue SSRI treatment is high and, as such, long-term treatment is commonly recommended. For some patients, engaging in exposure and response prevention (ERP) therapy can mitigate the risk of relapse that can follow discontinuation of an SSRI.
Q. What is the next step if the trial of an SSRI at both an adequate dosage and an adequate duration is deemed unsuccessful?
While studies vary, approximately 40–60% of patients with OCD will have a clinically significant response to their initial SSRI trial. For those who don’t, the first step is to ensure that the patient has been compliant with the medication (taking it as prescribed, including both at the right dosage and at the right intervals).
It is also important to ensure that the patient does not have other psychiatric or physical conditions that could potentially be responsible for the lack of response to the SSRI.
The two most common strategies employed when an initial SSRI trial at full dose is unsuccessful are:
Starting, or increasing the frequency of, ERP.
Switching to a different SSRI. This is typically recommended for two reasons: First, despite failure of one SSRI, patients will often have a positive response to the second SSRI, though it appears that this may be 10–20% less likely than the likelihood of response from the first trial. Secondly, SSRIs have a more favorable side-effect profile in comparison with other evidenced-based medication strategies used upon failure of the first SSRI.
If one or two SSRI trials fail, the most effective next steps are 1) switching from an SSRI to Clomipramine, 2) augmenting the SSRI with a second, adjunctive medication, or 3) switching to a second-line standalone medication.
Switching to Clomipramine
Clomipramine was the first medication to be found effective for treating OCD, and the first medication FDA-approved for OCD. Clomipramine is not an SSRI, but instead falls into a category known as tricyclic antidepressants (TCAs). Clomipramine is unique among the TCAs since it is a very potent serotonin reuptake inhibitor (SRI).
The question of whether Clomipramine is more effective for OCD than the SSRIs has been thoroughly researched. There does not appear to be substantive evidence to believe that Clomipramine is any more effective than SSRIs for adults with OCD. Head to head trials showed the SSRIs and Clomipramine had equal efficacy for OCD. This fact, along with Clomipramine having a worse side-effect profile than the SSRIs, is the reason that SSRIs are the standard first-line medication treatment for OCD.
Despite not being shown to be more effective than SSRIs, Clomipramine is commonly tried when patients fail trials on one or two SSRIs, as it has been found to be effective in some patients who don’t respond to SSRIs.
The most common adverse effects seen with Clomipramine are: dry mouth, urinary hesitancy, constipation, weight gain, and sexual dysfunction. More serious adverse effects include cardiac conduction delay and a lowering of the seizure threshold. For these reasons it is important that patients on Clomipramine have their drug levels measured, including both their Clomipramine levels and the levels of its active metabolite Desmethylclomipramine. Electrocardiograms (EKGs) must also be done at regular intervals, to monitor for rare but potential heart rhythm abnormalities.
Augmentation of an SSRI or Clomipramine with an Adjunctive Medication
Adjunctive Antipsychotics
The most common, and most evidenced-based, augmentation strategy is to add low-dose Dopamine Type 2 (D2) Receptor Antagonists (Blockers). These medications are known as antipsychotics because they were first developed and used to treat psychosis. This name persists even though these medications are now more often used for a myriad of conditions outside of psychosis.
When used to augment SSRIs in the treatment of OCD, the doses used are lower than those typically used for schizophrenia and bipolar disorder. Approximately one-third of patients who do not have satisfactory responses to an SSRI alone will respond when a low-dose D2 Receptor Antagonist is added.
There are multiple D2 Receptor Antagonists, but clinicians have the most evidence to support the newer, atypical antipsychotics, Aripiprazole and Risperidone. There is also some evidence to support the use of adjunctive Olanzapine or Quetiapine, or low-dose Haloperidol, one of the older, first-generation antipsychotics. However, those medications have a higher rate of short-term and long-term side effects.
Using antipsychotics on their own, without an SSRI, is not effective for OCD. Furthermore, the newer atypical antipsychotics, when used alone, can worsen or produce OCD symptoms - usually in people with schizophrenia or bipolar disorder.
Adjunctive Clomipramine
Another common augmentation strategy is augmenting an SSRI with Clomipramine. The logic here is that a patient may get the benefit of the SSRI and Clomipramine, while using lower doses of Clomipramine than required when using it alone, thereby minimizing the side effects associated with higher doses of Clomipramine. Studies have found this combination to be effective.
Adjunctive Glutamate Modulators
One important brain abnormality that is thought to underlie OCD in some patients is elevated activity of the neurotransmitter glutamate in the brain circuits that mediate OCD symptoms. This has led to promising research on various medications that modulate glutamate in different ways, including some anticonvulsants, such as lamotrigine and topiramate. No large-scale definitive studies have been conducted on these agents as of the time of this writing, but several smaller randomized, placebo-controlled studies and open trials have found some of these medications to be effective adjuncts to SSRIs for treatment-refractory OCD.
While there is less data on using glutamate modulators to augment SSRIs for OCD than there is for low-dose antipsychotic augmentation, there are instances when using glutamate modulators to augment SSRIs for OCD may be tried prior to low-dose antipsychotics, because glutamate modulators typically have better side-effect profiles. The glutamate modulators that are the most well studied as SSRI augmenters for OCD are Memantine, N-Acetylcysteine, Lamotrigine, Topiramate, Riluzole, and Ketamine.
Adjunctive Serotonin-3 Receptor Antagonists
Serotonin-3 receptor antagonists such as Ondansetron and Granisetron are commonly used for treatment of nausea and gastrointestinal disorders. However, numerous randomized, placebo-controlled studies and open trials have found that adding Ondansetron or Granisetron to an SRI is effective for treatment of OCD in individuals who did not have adequate response to SRIs alone.