Elsevier

Journal of Psychiatric Research

Volume 94, November 2017, Pages 23-28
Journal of Psychiatric Research

Buprenorphine augmentation improved symptoms of OCD, compared to placebo - Results from a randomized, double-blind and placebo-controlled clinical trial

https://doi.org/10.1016/j.jpsychires.2017.06.004Get rights and content

Highlights

  • Compared to adjuvant placebo, adjuvant buprenorphine improved symptoms of OCD.

  • Symptom improvements were observed from the third week on.

  • Opioid neurotransmission may be involved in the pathophysiology of OCD.

  • Buprenorphine did not show significant side effects.

  • Buprenorphine may be useful for future therapy of refractory OCD.

Abstract

Background

In the search for new psychopharmacologic options in the treatment of obsessive-compulsive disorders (OCD), some findings suggested that augmentation with buprenorphine, a partial-opioid agonist used to treat opioid addiction, moderate acute pain and moderate chronic pain, is worthy of consideration. Accordingly, to explore this possibility further, a double-blinded, placebo-controlled clinical trial was performed.

Method

A total of 43 patients (mean age: 34.41 years; SD = 6.58; 53.5% males) with refractory OCD and treated with SSRIs or clomipramine at therapeutic dosages were randomly assigned either to an adjuvant buprenorphine or to an adjuvant placebo condition. Patients completed the Yale-Brown-Obsessive-Compulsive Scale (Y-BOCS) at baseline, weeks 3, 9 and 12 (study completion). Buprenorphine (2–4 mg; sublingual) and placebo (tablets with identical shape, color, consistency, and scent) were given daily.

Results

Symptoms of obsessive-compulsive disorders decreased over time, but more so in the buprenorphine than in the placebo condition. Substantial improvements were observed up to week 3 and then 9. Response and partial response were observed in the buprenorphine at week 9 more than in the placebo condition. The advantage had disappeared by week 12.

Conclusions

The pattern of results suggests that adjuvant buprenorphine augmentation can reduce symptoms of obsessive-compulsive disorders after only three weeks, compared to a placebo. Adjuvant buprenorphine seems to accelerate symptom improvement.

Introduction

It is estimated that 1–3% of the population worldwide suffers from obsessive-compulsive disorders (OCD; Hirschtritt et al., 2017, Ruscio et al., 2010). Patients with OCD may report time-consuming, distressing and impairing persistent intrusive thoughts (obsessions), repetitive and ritualistic behaviors (compulsions), excessive anxiety, poor insight, and strong avoidance behavior, though, individual differences in intensity, frequency and duration of anxiety and avoidance, along with increased insight of disease are observed in clinical everyday life. In the DSM 5 compared to previous editions, OCD is no longer defined as anxiety disorder; OCD is classed as a disease in itself, and instead there is stress on the overlap between OCD and comorbid tics, hording and poor insight (Hirschtritt et al., 2017). Further, compared to the healthy, patients with OCD are at increased risk of a poor quality of life, impoverished social interaction, and loss of employment (Hollander, 1996). Not surprising, patients with OCD have a higher number of disability adjusted life-years (the number of years lost to disability), compared both to those who are healthy people and to patients with multiple sclerosis and Parkinson's Disease (Hirschtritt et al., 2017).

Both psychopharmacological and psychotherapeutic interventions are employed in the treatment of obsessive-compulsive disorders (Hirschtritt et al., 2017, Romanelli et al., 2014). Psychopharmacologic treatments mainly involve selective serotonin-reuptake inhibitors (SSRIs) as mainstay, followed by clomipramine (Haghighi et al., 2013, Wu et al., 2012). Further options are neuromodulatory interventions such as repetitive Transcranial Magnetic Stimulation (rTMS; Haghighi et al., 2015, Jahangard et al., 2016), or more experimental trials such as adjuvant memantine (Haghighi et al., 2013). Psychotherapeutic treatment involves cognitive-behavioral therapy, such as exposure therapy (Foa and McLean, 2016). In clinical practice, the two treatment strategies are often employed concomitantly. In the search for new pharmacologic treatment options (Grant et al., 2016), administration of opioids has attracted more interest within the last decade. Shapira et al. (1997) administered tramadol to six patients (mean age: 40.7 years; SD = 10.6; one male and five female patients) with refractory OCD. After two weeks of treatment, mean Y-BOCS score decreased from 27.8 to 20.7 points. Warneke (1997) and Goldsmith et al. (1999) reported single case study improvements with tramadol. Similarly, Liddell et al. (2013) reported results from a uncontrolled naturalistic study of seven different case studies of patients with refractory OCD. All patients were treated with 400 μg–600 μg of sublingual buprenorphine. Patients reported symptom improvements as early as two days after buprenorphine intake. Koran et al. (2005) performed a double-blind, case-control intervention study to investigate the influence of weekly morphine in 23 patients with refractory OCD, and observed that compared to lorazepam or to placebo, symptoms improved in the morphine group.

Overall there appears to be need for new treatment options for patients with OCD (Grant et al., 2016), and within the last 10 years, administration of opioids has attracted particular interest. Additionally, previous findings have mainly been based on single case studies (Goldsmith et al., 1999, Liddell et al., 2013, Warneke, 1997) though there has been one open label study (Shapira et al., 1997), and one double-blind clinical trial (Koran et al., 2005). The aim of the present study was to investigate the influence of buprenorphine adjuvant to a standard medication of SSRIs or clomipramine in patients with refractory OCD. The study involved a twelve-week double-blind and placebo controlled clinical trial.

Based on previous findings (Koran et al., 2005, Liddell et al., 2013), we expected symptom improvements in patients with adjuvant buprenorphine (+BUP), compared to an adjuvant placebo condition (+PLBO). The main outcome variables are the Y-BOCS scores and the response rates, as defined by Pallanti and Quercioli (2006) in more details below.

Section snippets

Study design

Eligible patients were approached from the Sina and Farshchian Hospitals (Hamadan, Iran) and consecutively enrolled in the present trial study (see details below). Specifically, outpatients diagnosed with obsessive-compulsive disorders (DSM 5, American Psychiatric Association, 2013) and under continuous treatment with SSRIs or clomipramine were approached to participate in the study. The study aims were fully explained, and patients gave their written informed consent. Next, they were randomly

Levels of obsessive-compulsive disorders, as measured with the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS)

Table 2, Table 3 report all descriptive and inferential statistical indices. Accordingly, the indices are not reported in the text.

Y-BOCS scores decreased significantly over time, but more so in the +BUP than in the +PLBO group (significant Time by Group-interaction). Post-hoc tests after Bonferroni-Holm corrections for p-values showed that there were differences between the two groups at weeks 3, 9 and 12. Compared to the +PLBO condition, those in the +BUP condition had significantly lower

Discussion

The key findings of the present randomized, double-blind and placebo-controlled study were that, among patients with refractory obsessive-compulsive disorders, buprenorphine adjuvant to a standard treatment with SSRI or clomipramine reduced OCD symptoms when compared to a placebo. The pattern of results adds to the current literature on the psychopharmacologic treatment of refractory OCD with opioids in that the results were obtained from a double-blind placebo controlled clinical trial.

Conclusions

The pattern of results from the present double-blind, randomized and placebo controlled clinical trial indicates that adjuvant buprenorphine produced statistically significant improvements in symptoms of obsessive-compulsive disorders within the first three weeks of treatment.

Funding

The entire study has been performed without external funding.

Authors contribution

MA, AR, AG, AS, MH, LJ, DSB, EHT, and SB designed the study.

MA, AR, AG, AS, MH, LJ, and DSB cared for the ethical approval.

MA, AR, AG, AS, MH, LJ, and DSB performed the study and were involved in data gathering and data entry.

MA, MH, DSB, EHT, and SB performed the statistical analysis.

DSB, EHT and SB wrote the draft.

MA, AR, AG, AS, MH, LJ commented on the draft.

DSB and SB integrated all authors’ comments and performed the final version.

MA, AR, AG, AS, MH, LJ, DSB, EHT, and SB agreed to submit

Conflict of interest

All authors declare no conflicts of interests.

Acknowledgement

We thank Nick Emler (University of Surrey, Surrey UK) for proofreading the manuscript.

References (20)

There are more references available in the full text version of this article.

Cited by (11)

  • Treatment-resistant OCD: Pharmacotherapies in adults

    2023, Comprehensive Psychiatry
    Citation Excerpt :

    Of note, responders' symptoms rapidly worsened when buprenorphine was stopped, and improved again after it was resumed. A subsequent 12-week RCT [9] randomized 43 participants with refractory OCD on stable and adequately dosed SRIs to either adjuvant sublingual buprenorphine (2–4 mg) or placebo. The Y-BOCS, obtained at baseline and weeks 3, 9, and 12, revealed substantial improvements at weeks 3 and 9 in the buprenorphine group compared to placebo, without further improvement at week 12.

  • Efficacy and tolerability of adjunctive gabapentin and memantine in obsessive compulsive disorder: Double-blind, randomized, placebo-controlled trial

    2018, Journal of Psychiatric Research
    Citation Excerpt :

    Psychopharmacologic treatments mainly involve selective serotonin-reuptake inhibitors (SSRIs) as the mainstay (Skapinakis et al., 2016), followed by clomipramine (Haghighi et al., 2013; Lack, 2012; Pallanti and Quercioli, 2006; Wu et al., 2012). Other options are neuro-modulatory interventions such as repetitive Transcranial Magnetic Stimulation (rTMS; Haghighi et al., 2015; Jahangard et al., 2016; Shayganfard et al., 2016), and more experimental treatments such as adjuvant buprenorphine (Ahmadpanah et al., 2017; Liddell et al., 2013), adjuvant memantine (Ghaleiha et al., 2013; Haghighi et al., 2013; Hirschtritt et al., 2017; Modarresi et al., 2017; Wu et al., 2012), adjuvant N-Acetyl Cysteine (Oliver et al., 2015; Sarris et al., 2015), and, more recently, adjuvant gabapentin (Onder et al., 2008). Gabapentin is an anticonvulsant mainly used to treat epilepsy (Nevitt et al., 2017), refractory chronic cough (Ryan et al., 2018), neuropathic pain (Alles and Smith, 2018), and restless-legs syndrome (Iftikhar et al., 2017; Kim and Hartzema, 2018).

  • Oral N-acetylcysteine in the treatment of obsessive-compulsive disorder: A systematic review of the clinical evidence

    2018, Progress in Neuro-Psychopharmacology and Biological Psychiatry
    Citation Excerpt :

    Consequently, the investigation for more targeted pharmacologic agents and new augmentation strategies are crucial. In this way, some studies have been published focusing in the potential effect of other drugs, such as buprenorphine and memantine, and also non-pharmacological therapies, like electroconvulsive therapy (ECT), with auspicious results (Ahmadpanah et al., 2017; Haghighi et al., 2013; Manhas et al., 2016). Regarding this matter, in 2006, Lafleur and colleagues (Bonanomi and Gazzaniga, 1980) found promising results with the use of N-acetylcysteine (NAC).

View all citing articles on Scopus
View full text