Obsessive-Compulsive Disorder Medication
- Author: William M Greenberg, MD; Chief Editor: David Bienenfeld, MD more...
Only antidepressants that potently inhibit presynaptic reuptake of serotonin appear to be effective in treating obsessive-compulsive disorder (OCD). Clomipramine (Anafranil) is the only tricyclic antidepressant (TCA) with this quality. The selective serotonin reuptake inhibitors (SSRIs) are also effective. SSRIs have the advantages of ease of dosing and low toxicity in overdose. Available SSRIs include fluoxetine (Prozac), fluvoxamine (Luvox), paroxetine (Paxil), citalopram (Celexa), escitalopram (Lexapro), and sertraline (Zoloft).
SSRIs or clomipramine should be advanced as tolerated to a therapeutic dose. Clinical response may take 6-10 weeks to become apparent. The clinician should review adequacy of dose, duration of therapy, and compliance before deciding that a medication is ineffective.
SSRIs are generally preferred over clomipramine in treating OCD. The adverse effect profiles of SSRIs are less prominent, so improved compliance is promoted. SSRIs do not have the cardiac arrhythmia risk associated with TCAs; however, citalopram causes dose-dependent QT prolongation.[36, 37] Arrhythmia risk is especially pertinent in overdose, and suicide risk must always be considered when treating a child or adolescent with mood disorder.
Antipsychotics, such as haloperidol, olanzapine, and risperidone, have been used with some success in augmenting SSRIs in patients with OCD, particularly in patients with comorbid Tourette disorder or other tic disorders.
A Cochrane review found some evidence of efficacy for quetiapine or risperidone as a general augmentation strategy (not specifically for those with comorbid tics). However, heterogeneity was noted in doses used and in response, and the number of subjects in these studies was generally small
The dual serotonin-norepinephrine reuptake inhibitor antidepressants (SNRIs) venlafaxine (Effexor) and duloxetine (Cymbalta) may also have efficacy in OCD, and they have safety and tolerability profiles comparable to those of the SSRIs. However, neither has yet been FDA-approved specifically for treatment of OCD.
Complications of pharmacologic treatment
Physicians are advised to be aware of the following information and to use appropriate caution when considering treatment with SSRIs in the pediatric population.
In December 2003, the UK Medicines and Healthcare Products Regulatory Agency (MHRA) issued an advisory that most SSRIs are not suitable for use by persons younger than 18 years for treatment of "depressive illness." After review, this agency decided that the risks to pediatric patients outweighed the benefits of treatment with SSRIs, except fluoxetine (Prozac), which appeared to have a positive risk-benefit ratio in the treatment of depressive illness in patients younger than 18 years.
In October 2003, the FDA issued a public health advisory regarding reports of suicidality in pediatric patients being treated with antidepressant medications for major depressive disorder. This advisory reported suicidality (ideation and attempts) in clinical trials of various antidepressant drugs in pediatric patients. The FDA asked that additional studies be performed, because suicidality occurred in treated and untreated patients with major depression and thus could not be definitively linked to drug treatment.
Upon further analysis of pooled clinical trial data, suicidality was reportedly increased in children and adolescents being treated with SSRIs for depression (approximately 2% for those treated with placebo vs 4% for those on SSRIs, although no actual suicides occurred in either group). These clinical trials were unfortunately not designed to specifically and clearly assess suicidal thoughts and behaviors and therefore included events that were not readily classified.
The FDA issued a public health advisory in October of 2004 mandating a black box warning for antidepressants. Antidepressant treatment of children and adolescents with depression then significantly decreased over the next 2 years, although apparently so did suicides for this population. In 2007, the FDA extended its warning to young adults.
Currently, evidence does not exist to associate an increased risk of suicide in patients with OCD and/or other anxiety disorders being treated with SSRIs. However, physicians should closely attend to whether treated patients have unusual, uncomfortable adverse reactions (eg, akathisia) or if they might have comorbid bipolar disorder (which may involve only subtle hypomanic episodes), as antidepressant use seems to occasionally be associated with triggering dysphoria and, sometimes, manic episodes in such individuals.
Children, adolescents, and young adults being treated with antidepressants should be closely and frequently monitored, particularly early in treatment, for any suicidal ideation or actions.
Selective Serotonin Reuptake Inhibitors
First-line pharmacologic treatments consist of selective serotonin reuptake inhibitors (SSRIs). SSRIs have the advantages of ease of dosing and low toxicity in overdose. Available SSRIs include fluoxetine (Prozac), fluvoxamine (Luvox), paroxetine (Paxil), citalopram (Celexa), escitalopram (Lexapro), and sertraline (Zoloft). SSRIs are generally preferred over clomipramine in treating OCD. The adverse effect profiles of SSRIs are less prominent, so improved compliance is promoted. SSRIs do not have the cardiac arrhythmia risk associated with TCAs, however, dose-dependent QT prolongation has been reported with citalopram. Because of the risk for QT prolongation, citalopram is contraindicated in individuals with congenital long QT syndrome and the dose should not exceed 40 mg/d.[36, 37] Arrhythmia risk is especially pertinent in overdose, and suicide risk must always be considered when treating a child or adolescent with a mood disorder.
Fluoxetine selectively inhibits presynaptic serotonin reuptake with minimal or no effect in the reuptake of norepinephrine or dopamine. Selective serotonin inhibitors such as fluoxetine have less sedation, cardiovascular, and anticholinergic effects than the TCAs.
Citalopram enhances serotonin activity due to selective reuptake inhibition at the neuronal membrane. Citalopram is FDA approved for depression but has been used for the treatment of anxiety disorders. SSRIs are the antidepressants of choice due to minimal anticholinergic effects.
Paroxetine is a potent selective inhibitor of neuronal serotonin reuptake. It also has a weak effect on norepinephrine and dopamine neuronal reuptake.
Sertraline selectively inhibits presynaptic serotonin reuptake at the neuronal membrane. It is FDA approved for the treatment of OCD, posttraumatic stress disorder, panic disorder, and social anxiety.
Fluvoxamine enhances serotonin activity by selective reuptake inhibition at the neuronal membrane. It does not significantly bind to alpha-adrenergic, histamine, or cholinergic receptors and thus has fewer adverse effects than TCAs. It is FDA-approved for OCD in children (8-17 y) and adults.
Escitalopram is an SSRI and S-enantiomer of citalopram. Its mechanism of action is thought to be potentiation of serotonergic activity in the CNS, resulting from inhibition of CNS neuronal reuptake of serotonin.
Tricyclic are a class of antidepressants that work by inhibiting the reuptake of norepinephrine or serotonin at presynaptic neurons.
Clomipramine is FDA approved to treat obsessions and compulsions in OCD. It is a dibenzazepine compound belonging to family of TCAs. It inhibits the membrane pump mechanism responsible for uptake of norepinephrine and serotonin in adrenergic and serotonergic neurons. Clomipramine affects serotonin uptake, while it affects norepinephrine uptake when converted into its metabolite desmethylclomipramine.
Desipramine is a TCA that has norepinephrine and serotonin reuptake-inhibition properties. It is not FDA approved for OCD; however, it has shown beneficial effects, especially when combined with SSRIs.
Serotonin Norepinephrine Reuptake Inhibitor
The dual serotonin-norepinephrine reuptake inhibitor antidepressants (SNRIs) venlafaxine (Effexor) and duloxetine (Cymbalta) may also have efficacy in OCD, and they have safety and tolerability profiles comparable to those of the SSRIs. However, neither has yet been FDA approved specifically for the treatment of OCD.
Venlafaxine is a serotonin/norepinephrine reuptake inhibitor. It may treat depression by inhibiting neuronal serotonin and norepinephrine reuptake. In addition, it causes beta-receptor down-regulation. It is used in the treatment of OCD; however, it is not FDA approved for this indication.
Duloxetine is a potent inhibitor of neuronal serotonin and norepinephrine reuptake. Its antidepressive action is theorized to be due to serotonergic and noradrenergic potentiation in the CNS.
Antipsychotics, such as haloperidol, olanzapine, and risperidone, have been used with some success in augmenting SSRIs in patients with OCD, particularly in patients with comorbid Tourette disorder or other tic disorders. These agents are not FDA approved for the treatment of OCD but may be beneficial.
Risperidone is an atypical antipsychotic that has high affinity for both serotonergic and dopaminergic receptors. It also binds to alpha1-adrenergic receptors and, with lower affinity, to H1-histaminergic and alpha2-adrenergic receptors. It is approved to treat patients with bipolar mania, schizophrenia, and irritability associated with autistic disorder.
Olanzapine is an atypical antipsychotic agent approved for the treatment of bipolar disorder, schizophrenia, and treatment-resistant depression. It may be helpful in the treatment of OCD; however, it is not FDA approved for this indication.
Lithium is an antipsychotic agent that is indicated for bipolar disorder. It influences the reuptake of serotonin and/or norepinephrine at cell membranes. It has been used in the treatment of OCD; however, it is not FDA approved for this indication.
Haloperidol is an antipsychotic agent that exerts its effects through blocking dopamine receptors. It has been used to augment SSRIs in patients with OCD.
Augmentation with antianxiety agents such as buspirone may be beneficial in patients with OCD.
Buspirone is an antianxiety agent not chemically or pharmacologically related to the benzodiazepines, barbiturates, or other sedative or anxiolytic drugs. It is a 5-HT1 agonist with serotonergic neurotransmission and some dopaminergic effects in the CNS.
Karno M, Golding JM, Sorenson SB, Burnam MA. The epidemiology of obsessive-compulsive disorder in five US communities. Arch Gen Psychiatry. 1988 Dec. 45(12):1094-9. [Medline].
Goodman WK, Price LH, Rasmussen SA, Mazure C, Fleischmann RL, Hill CL, et al. The Yale-Brown Obsessive Compulsive Scale. I. Development, use, and reliability. Arch Gen Psychiatry. 1989 Nov. 46(11):1006-11. [Medline].
American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Arlington, VA: American Psychiatric Association; 2013.
Pepper J, Hariz M, Zrinzo L. Deep brain stimulation versus anterior capsulotomy for obsessive-compulsive disorder: a review of the literature. J Neurosurg. 2015 May. 122 (5):1028-37. [Medline].
Andrade C. Ondansetron augmentation of serotonin reuptake inhibitors as a treatment strategy in obsessive-compulsive disorder. J Clin Psychiatry. 2015 Jan. 76 (1):e72-5. [Medline].
Coric V, Taskiran S, Pittenger C, Wasylink S, Mathalon DH, Valentine G, et al. Riluzole augmentation in treatment-resistant obsessive-compulsive disorder: an open-label trial. Biol Psychiatry. 2005 Sep 1. 58(5):424-8. [Medline].
Greenberg WM, Benedict MM, Doerfer J, Perrin M, Panek L, Cleveland WL, et al. Adjunctive glycine in the treatment of obsessive-compulsive disorder in adults. J Psychiatr Res. 2009 Mar. 43(6):664-70. [Medline].
Haghighi M, Jahangard L, Mohammad-Beigi H, Bajoghli H, Hafezian H, Rahimi A, et al. In a double-blind, randomized and placebo-controlled trial, adjuvant memantine improved symptoms in inpatients suffering from refractory obsessive-compulsive disorders (OCD). Psychopharmacology (Berl). 2013 Mar 23. [Medline].
Ghaleiha A, Entezari N, Modabbernia A, Najand B, Askari N, Tabrizi M, et al. Memantine add-on in moderate to severe obsessive-compulsive disorder: randomized double-blind placebo-controlled study. J Psychiatr Res. 2013 Feb. 47(2):175-80. [Medline].
Rodriguez CI, Kegeles LS, Levinson A, Feng T, Marcus SM, Vermes D, et al. Randomized Controlled Crossover Trial of Ketamine in Obsessive-Compulsive Disorder: Proof-of-Concept. Neuropsychopharmacology. 2013 Jun 19. [Medline].
Greenberg BD, Malone DA, Friehs GM, Rezai AR, Kubu CS, Malloy PF, et al. Three-year outcomes in deep brain stimulation for highly resistant obsessive-compulsive disorder. Neuropsychopharmacology. 2006 Nov. 31(11):2384-93. [Medline].
Mallet L, Polosan M, Jaafari N, Baup N, Welter ML, Fontaine D, et al. Subthalamic nucleus stimulation in severe obsessive-compulsive disorder. N Engl J Med. 2008 Nov 13. 359(20):2121-34. [Medline].
Jung HH, Kim CH, Chang JH, Park YG, Chung SS, Chang JW. Bilateral anterior cingulotomy for refractory obsessive-compulsive disorder: Long-term follow-up results. Stereotact Funct Neurosurg. 2006. 84(4):184-9. [Medline].
Stetka B, Correll, C. A Guide to DSM-5: Hoarding, Skin-Picking, and Rethinking OCD. Available. Medscape Medical News. Available at http://www.medscape.com/viewarticle/803884_7. Accessed: July 1, 2013.
APA. Obsessive-Compulsive and Related Disorders. Available at http://www.dsm5.org/Documents/Obsessive%20Compulsive%20Disorders%20Fact%20Sheet.pdf.. Accessed: July 1, 2013.
Greist JH, Jefferson JW, Kobak KA, Katzelnick DJ, Serlin RC. Efficacy and tolerability of serotonin transport inhibitors in obsessive-compulsive disorder. A meta-analysis. Arch Gen Psychiatry. 1995 Jan. 52(1):53-60. [Medline].
Kobak KA, Greist JH, Jefferson JW, Katzelnick DJ, Henk HJ. Behavioral versus pharmacological treatments of obsessive compulsive disorder: a meta-analysis. Psychopharmacology (Berl). 1998 Apr. 136(3):205-16. [Medline].
Bloch MH, Landeros-Weisenberger A, Kelmendi B, Coric V, Bracken MB, Leckman JF. A systematic review: antipsychotic augmentation with treatment refractory obsessive-compulsive disorder. Mol Psychiatry. 2006 Jul. 11(7):622-32. [Medline].
Baxter LR Jr, Schwartz JM, Bergman KS, Szuba MP, Guze BH, Mazziotta JC, et al. Caudate glucose metabolic rate changes with both drug and behavior therapy for obsessive-compulsive disorder. Arch Gen Psychiatry. 1992 Sep. 49(9):681-9. [Medline].
Pittenger C, Krystal JH, Coric V. Glutamate-modulating drugs as novel pharmacotherapeutic agents in the treatment of obsessive-compulsive disorder. NeuroRx. 2006 Jan. 3(1):69-81. [Medline].
Wu K, Hanna GL, Rosenberg DR, Arnold PD. The role of glutamate signaling in the pathogenesis and treatment of obsessive-compulsive disorder. Pharmacol Biochem Behav. 2012 Feb. 100(4):726-35. [Medline]. [Full Text].
van Grootheest DS, Cath DC, Beekman AT, Boomsma DI. Twin studies on obsessive-compulsive disorder: a review. Twin Res Hum Genet. 2005 Oct. 8(5):450-8. [Medline].
Carey G, Gottesman I. Twin and family studies of anxiety, phobic, and obsessive disorders. Klein DF, Rabkin JG. Anxiety: New Research and Changing Concepts. New York: Raven Press; 2000.
Arnold PD, Rosenberg DR, Mundo E, Tharmalingam S, Kennedy JL, Richter MA. Association of a glutamate (NMDA) subunit receptor gene (GRIN2B) with obessive-compulsive disorder: a preliminary study. Psychopharmacology. August 2004. 174:530-538.
Arnold PD, Sicard T, Burroughs E, Richter MA, Kennedy JL. Glutamate transporter gene SLC1A1 associated with obsessive-compulsive disorder. Arch Gen Psychiatry. 2006 Jul. 63(7):769-76. [Medline].
Denys D, Van Nieuwerburgh F, Deforce D, Westenberg H. Association between the dopamine D2 receptor TaqI A2 allele and low activity COMT allele with obsessive-compulsive disorder in males. Eur Neuropsychopharmacol. 2006 Aug. 16(6):446-50. [Medline].
Dickel DE, Veenstra-VanderWeele J, Cox NJ, Wu X, Fischer DJ, Van Etten-Lee M, et al. Association testing of the positional and functional candidate gene SLC1A1/EAAC1 in early-onset obsessive-compulsive disorder. Arch Gen Psychiatry. 2006 Jul. 63(7):778-85. [Medline].
Lin PY. Meta-analysis of the association of serotonin transporter gene polymorphism with obsessive-compulsive disorder. Prog Neuropsychopharmacol Biol Psychiatry. 2007 Apr 13. 31(3):683-9. [Medline].
Rapoport JL. The Boy Who Couldn't Stop Washing: The Experience and Treatment of Obsessive-Compulsive Disorder. paperback. New York: Penguin Putnam; 2001.
[Guideline] American Psychiatric Association Work Group on Obsessive-Compulsive Disorder. Practice guideline for the treatment of patients with obsessive-compulsive disorder. Am J Psychiatry. July 2007. 164(suppl):1-56. [Full Text].
Foa EB, Wilson R. Stop Obsessing!: How to Overcome Your Obsessions and Compulsions. Revis ed. New York: Bantam Dell; 2001.
First MB, Spitzer RL, Gibbon M, Williams JBW. Structured Clinical Interview for DSM-IV-TR Axis I Disorders - Patient Edition (SCID-I/P, 11/2002 revision). New York: Biometrics Research Department, New York State Psychiatric Institute; November 2002.
Berlin HA, Koran LM, Jenike MA, et al. Double-blind, placebo-controlled trial of topiramate augmentation in treatment-resistant obsessive-compulsive disorder. J Clin Psychiatry. 2011 May. 72(5):716-21. [Medline].
Simpson HB, Wetterneck CT, Cahill SP, Steinglass JE, Franklin ME, Leonard RC, et al. Treatment of obsessive-compulsive disorder complicated by comorbid eating disorders. Cogn Behav Ther. 2013 Mar. 42(1):64-76. [Medline].
Grayson J. Freedom From Obsessive Compulsive Disorder: A Personalized Recovery Program for Living With Uncertainty. New York: Berkley Publishing Group; 2004.
Celexa (citalopram hydrobromide) [package insert]. St. Louis, Missouri: Forest Pharmaceuticals, Inc. August, 2011. Available at [Full Text].
US Food and Drug Administration. Celexa (citalopram hydrobromide): Drug safety communication – abnormal heart rhythms associated with high doses. Available at http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm269481.htm. Accessed: August 24, 2011.
Komossa K, Depping AM, Meyer M, Kissling W, Leucht S. Second-generation antipsychotics for obsessive compulsive disorder. Cochrane Database Syst Rev. 2010 Dec 8. 12:CD008141. [Medline].
FDA Public Health Advisory: Suicidality in Children and Adolescents Being Treated With Antidepressant Medications. FDA Website. October 15, 2004. 1-3. [Full Text].
FDA Proposes New Warnings About Suicidal Thinking, Behavior in Young Adults Who Take Antidepressant Medications. FDA Website. May 2, 2007. 1-3. [Full Text].
A Message From APA President Dilip Jeste, M.D., on DSM-5. Available at http://www.psychnews.org/files/DSM-message.pdf. Accessed: December 1, 2012.
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4th Edition, Text Revision (DSM-IV-TR). Washington, DC: American Psychiatric Association; 2000.
Bartz JA, Hollander E. Is obsessive-compulsive disorder an anxiety disorder?. Prog Neuropsychopharmacol Biol Psychiatry. 2006 May. 30(3):338-52. [Medline].
Bienvenu OJ, Samuels JF, Wuyek LA, Liang KY, Wang Y, Grados MA, et al. Is obsessive-compulsive disorder an anxiety disorder, and what, if any, are spectrum conditions? A family study perspective. Psychol Med. 2012 Jan. 42(1):1-13. [Medline].
Brooks M. Adjunctive CBT First Choice for Refractory OCD. Medscape Medical News. Sep 11 2013. [Full Text].
Dell'Osso B, Altamura AC, Allen A, Marazziti D, Hollander E. Epidemiologic and clinical updates on impulse control disorders: a critical review. Eur Arch Psychiatry Clin Neurosci. 2006 Dec. 256(8):464-75. [Medline]. [Full Text].
Melville NA. CBT beats adjunctive antipsychotic for refractory OCD. Medscape Medical News. April 11, 2013. [Full Text].
Simpson HB, Foa EB, Liebowitz MR, et al. Cognitive-Behavioral Therapy vs Risperidone for Augmenting Serotonin Reuptake Inhibitors in Obsessive-Compulsive Disorder: A Randomized Clinical Trial. JAMA Psychiatry. Sep 11 2013. [Medline].
|Obsessions||Commonly Associated Compulsions|
|Fear of contamination||Washing, cleaning|
|Need for symmetry, precise arranging||Ordering, arranging, balancing, straightening until "just right"|
|Unwanted sexual or aggressive thoughts or images||Checking, praying, “undoing” actions, asking for reassurance|
|Doubts (eg, gas jets off, doors locked)||Repeated checking behaviors|
|Concerns about throwing away something valuable||Hoarding|