The first-line treatment for adult obsessive-compulsive disorder (OCD) is typically a prescription for an SRI (serotonin reuptake inhibitor) drug, medications most often used to treat depression. SRIs are the only medications so far approved by the FDA for treating OCD.

While SRIs help many OCD patients, “most continue to exhibit clinically significant symptoms affecting their quality of life,” according to a research team co-led by Helen Blair Simpson, M.D., Ph.D., a 2010 BBRF Independent Investigator and 2005 Young Investigator at Columbia University and the New York State Psychiatric Institute.

Patients who continue to suffer OCD symptoms can switch to another SRI medicine and/or augment their SRI treatment with another medication or a form of therapy called exposure/response prevention (EX/RP).

Treatment of OCD with EX/RP typically consists of 15-20 individual therapy sessions of about 90 minutes each. The therapist helps the patient with gradual and systematic exposures to obsessions or objects, situations, mental images and thoughts, or other stimuli that trigger anxiety and obsessions. The therapist also works with the patient to reduce or eliminate responding to obsessions with compulsive behaviors or rituals. Many who have experienced positive results have been able to use EX/RP strategies to manage OCD symptoms over the long-term.

Dr. Simpson and Edna B. Foa, Ph.D., of the University of Pennsylvania Perelman School of Medicine, wanted to know whether OCD patients taking an SRI medication who are able to attain “wellness” after augmenting that therapy with EX/RP treatments can safely “taper” their SRI dose to the point where they cease taking the medicine altogether.

Together, they and their research teams conducted a randomized clinical trial in which 51 OCD patients achieving wellness after upto 25 EX/TR therapy sessions tapered their SRI dose, while 50 patients also attaining wellness after EX/RP continued taking their SRI medicine. The trial involved repeated assessment over 24 weeks of not only OCD symptoms in each participant, but also accompanying symptoms of depression, where present, as well as overall quality of life. Wellness was defined relative to a scale that is commonly used to assess OCD symptom severity. Results of the trial were reported in JAMA Psychiatry.

The 101 participants were randomly assigned to the two groups. Those in the “taper” group received decreasing dosages of their SRI over the first 4 weeks of the trial (25% lower dosage each week), after which they were given identical-looking but inactive placebo pills. Neither the participants nor those who treated and monitored their symptoms knew which groups the participants were assigned to.

The trial, which took 5 years to complete, resulted in a finding of “noninferior outcomes” for the “taper” strategy, based on clinical measures for OCD, depression, and quality of life. By this, the researchers mean that those who stopped receiving active SRI medicines during the 24 weeks of the trial had outcomes on these measures that did not significantly differ at week 24 from participants who continued to take their SRI medicines throughout the trial.

Patients in both groups exhibited “small, clinically insubstantial worsening in symptoms” over the 24 weeks, the researchers noted. This is to say, OCD symptoms, on average, got a bit worse in both groups, as did depression scores and quality of life scores. Yet about half of patients in both groups—SRI “taper” and “continuation”—maintained wellness, as measured by the standard OCD symptom severity test.

On the other hand, significantly more patients in the “taper group” were removed from the study for overall clinical worsening as rated by their clinician compared with those who stayed on their SRI medicine (45% versus 24%); this seemed to occur in those who tapered off of SRI medicines that have a short biochemical “half-life.” Half-life is a measure of how long a medicine persists in the system after a dose is taken. Patients taking SRIs with short half-lives (26 hours of less) were presumably more sensitive to the withdrawal of their SRI medicine, and thus were more likely to report symptoms of some kind, whether related to OCD, depression, or related to withdrawal from the medicine.

The team says that the next important step is to determine which individuals can and cannot safely taper off their SRI medication, so that clinicians can provide accurate advice to their patients. The team also hopes that the “taper” strategy will be tested in children with OCD.

In general, however, the team concluded on the basis of their results that “after successful augmentation with EX/RP, patients who achieve wellness after EX/RP could, on average, discontinue their SRI with non-inferior outcomes on measures of OCD, depression and quality of life, compared with those who continued their SRI.” Given the higher rate of overall clinical worsening that they observed, the team recommends careful clinical monitoring in those who taper off SRIs.

The research team also included: Michael Wheaton, Ph.D., 2018 BBRF Young Investigator; Shari Steinman, Ph.D., 2015 BBRF Young Investigator; Chang-Gyu Hahn, M.D., Ph.D., 2010 BBRF Independent Investigator, 2002 and 2000 Young Investigator; and Bin Xu, Ph.D., 2013 and 2008 BBRF Young Investigator.