Improvement of Obsessive-compulsive Disorder with Divalproex and Lamotrigine in Two Patients with Bipolar II Disorder

We describe two cases of patients with bipolar II disorder and comorbid obsessive-compulsive disorder who received treatment with mood stabilizers (lamotrigine and divalproex). The patients reported significant improvements of both conditions.

Divalproex (DVP) and lamotrigine (LMT) have been used as mood stabilizers for the treatment and the prevention of recurrence of bipolar disorder. The first is recommended for treatment of acute mania and maintenance treatment of bipolar disorder (BD) and the latter is useful for prevention of bipolar depressive episodes.

The lifetime prevalence of bipolar spectrum disorders is 4.4–6.5% of the general population [1] [12]. Comorbidity of obsessive compulsive disorder (OCD) was found in 10–25% of bipolar I and II patients [12] [14], with a negative impact on the course and treatment of BD [12].

The treatment of patients with both conditions (BD and OCD) is a therapeutic dilemma because effective treatments of OCD, such as high-dose serotonin reuptake inhibitors (SRIs), could cause switching to mania and rapid cycling [11]. Furthermore, the clinical trials that have led to the approval of SRIs for the treatment of OCD exclude patients with bipolar disorder as a rule. Atypical antipsychotics, which are effective for the treatment of bipolar disorder, have emerged as a therapeutic alternative in refractory OCD, but can be associated with significant side-effects and limited efficacy [3] [6]. There are no controlled trials for comorbidities; thus, therapeutic options with minor risks have high clinical relevance in this population.

Regarding anticonvulsants, there is a report on 8 refractory OCD patients treated with lamotrigine as add-on to SRIs, with 1 responder [8], another report of improvement with valproate monotherapy in one patient with OCD [4] and another report of improvement of treatment-resistant obsessive-compulsive disorder (OCD) with a pharmacological augmentation of topiramate plus paroxetine [7]. Zink et al. [16] (2007) described one patient with schizophrenia who developed obsessive-compulsive symptoms after clozapine was initiated and improved with valproic acid.

We describe two cases of patients with the diagnoses of BD and OCD who presented with improvements of mood and anxiety symptoms under mood-stabilizers only.

A 36-year-old white woman with previous diagnoses of panic disorder (PD) and recurrent depressive episodes had undergone treatment with antidepressants since 18 years of age, with partial response. Diagnostic evaluation revealed that she later developed episodes of irritable mood, overactivity, racing thoughts, pressure of speech, decrease need for sleep, paranoid symptoms, buying sprees and anger attacks that lasted up to one month, alternating with depressive episodes, therefore fulfilling the DSM-IV diagnostic criteria for bipolar II disorder. She had obsessive-compulsive disorder since 10 years of age, especially with fear of contamination, repetitive behaviours of excessive cleaning and checking door locks. Under treatment with fluoxetine 20 mg her mood was unstable, with no impact on OCD symptoms.

She started treatment with lamotrigine up to 100 mg/d with a significant improvement of depressive symptoms, irritability and obsessive-compulsive symptoms. However, panic symptoms increased and paroxetine up to 20 mg was added, triggering a hypomanic episode. Paroxetine was discontinued and divalproex up to 500 mg/d was started. Currently, the patient is on treatment with lamotrigine 100 mg/d and divalproex 500 mg/d with improvement of BD, OCD and panic disorder. Her score on the Yale-Brown Obsessive-Compulsive Scale (YBOCS) decreased from 46 prior to treatment to 04 after six months. She remained stable for two years.

A 31-year-old white man had bipolar II disorder, with anger attacks, overactivity, racing thoughts in hypomanic episodes that lasted up to one week and alternated with episodes of atypical depression. He has a family history of BD and reported a switch to mania with venlafaxine in the past. He met the DSM-IV criteria for alcohol abuse and OCD. He had obsessive-compulsive symptoms since 15 years of age and mood symptoms since 26 years of age. The most prominent symptoms of OCD were repetitive behaviour of checking door locks, electrical outlets and hoarding. He was referred to psychiatric evaluation by his psychologist who had been conducting cognitive-behavioural psychotherapy for one year without good response.

Treatment with divalproex up to 1 000 mg/d was initiated and after six weeks the patient reported a significant improvement of alcohol abuse and obsessive-compulsive symptoms. His YBOCS score declined from 23 prior to treatment to 04. He stopped the mood stabilizer and the symptoms returned, but after the reintroduction of medication he improved again. He has been symptom-free for 18 months.

In agreement with comorbidity studies, some authors have proposed a distinction between bipolar/cyclothymic and unipolar OCD [2] [6]. Indeed, the results of Angst et al. [2] (2005) suggest that OCD is more comorbid with bipolar spectrum disorders than with unipolar depression and Merikangas et al. [12] (2007) have found an odds ratio of 16.7–21.4 for OCD in patients with bipolar I and II disorders, which was the highest odds ratio for a comorbidity in bipolar patients. Considering such a level of comorbidity between these disorders, along with treatment difficulties with SRIs in those with bipolar disorder, this is a clearly an understudied clinical reality, particularly in terms of treatment. Since the efficacy of SRI has been established in patients with OCD without bipolar disorder comorbidity, their efficacy cannot be assumed for patients with this comorbidity. A logical approach would be to evaluate the efficacy of mood stabilizers alone in these patients, which has not been systematically done to the best of our knowledge. Surprisingly, the few studies that have tested the efficacy of mood stabilizers in OCD have been add-on treatments to SRI and there is only one case report of valproate monotherapy for OCD without bipolar disorder [4] and a report of 2 patients with episodic OCD who responded to lithium monotherapy [15].

It is interesting to note that the onset of OCD predated that of bipolar disorder in both patients, as reported in many cases [17]. However, she responded to valproate and lamotrigine and not to fluoxetine. We have proposed that temperamental or emotional dysregulation may underlie the observed pattern of comorbidities in psychiatry, with particular relevance for some disorders such as OCD, which may be associated with high fear, high anger and/or high control as temperamental traits [9]. Thus, treatment aimed at this underlying emotional dysregulation could bring about improvement in many comorbidities simultaneously [10]. The patients with this comorbidity could represent a distinct form of OCD that differs in neurobiology, course, symptoms and response to treatment [6].

These present reports on the efficacy of lamotrigine and divalproex without SRIs or atypical antipsychotics in patients with OCD and BD suggest that these drugs may be adequate, at least for some patients. Well-designed controlled trials with mood stabilizers should be conducted in patients with bipolar comorbidities as these conditions are a rule rather than the exception in clinical practice.

References

• 1 Angst J. The emerging epidemiology of hypomania and bipolar II disorder.  J Affect Disord. 1998;  50 143-151
• 2 Angst J, Gamma A, Endrass J. et al . Obsessive-compulsive syndromes and disorders: significance of comorbidity with bipolar and anxiety syndromes.  Eur Arch Psy Clin Neurosci. 2005;  255 65-71
• 3 Bloch MH, Landeros-Weisenberger A, Kelmendi B. et al . A systematic review: antipsychotic augmentation with treatment refractory obsessive-compulsive disorder.  Mol Psychiat. 2006;  11 622-632
• 4 Corá-Locatelli G, Greenberg BD, Martin JD. et al . Valproate monotherapy in an SRI-intolerant patient.  J Clin Psychiat. 1998;  59 82
• 5 Dell’Osso B, Altamura AC, Mundo E. et al . Diagnosis and treatment of obsessive-compulsive disorder and related disorders.  Int J Clin Pract. 2007;  61 98-104
• 6 Hantouche EG, Angst J, Demonfaucon C. et al . Cyclothymic OCD: a distinct form?.  J Affect Disord. 2003;  75 1-10
• 7 Hollander E, Dell’Osso B. Topiramate plus paroxetine in treatment-resistant obsessive-compulsive disorder.  Int Clin Psychopharmacol. 2006;  21 189-191
• 8 Kumar TC, Khanna S. Lamotrigine augmentation of serotonin re-uptake inhibitors in obsessive-compulsive disorder.  Aust N Z J Psychiat. 2000;  34 527-528
• 9 Lara DR, Pinto O, Akiskal K. et al . Toward an integrative model of the spectrum of mood, behavioral and personality disorders base don fear and anger traits: I. Clinical implications.  J Affect Disord. 2006;  94 67-87
• 10 Lara DR, Akiskal HS. Toward an integrative model of the spectrum of mood, behavioral and personality disorders based on fear and anger traits: II. Implications for neurobiology, genetics and psychopharmacological treatment.  J Affect Disord. 2006;  94 89-103
• 11 Math SB, Janardhan Reddy YC. Issues in the pharmacological treat-ment of obsessive-compulsive disorder.  Int J Clin Pract. 2007;  61 1188-1197
• 12 Merikangas KR, Akiskal HS, Angst J. et al . Lifetime and 12-month prevalence of bipolar spectrum in the National Comorbidity Survey replication.  Arch Gen Psychiat. 2007;  64 544-552
• 13 Sasson Y, Chopra M, Harrari E. et al . Bipolar comorbidity: from diagnostic dilemmas to therapeutic challenge.  Int J Neuropsychopharmacol. 2003;  6 139-144
• 14 Simon NM, Otto MW, Wisniewski SR. et al . Anxiety disorder comorbidity in bipolar disorder patients:data from the first 500 participants in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD).  Am J Psychiat. 2004;  161 2222-2229
• 15 Swartz CM, Shen WW. Is episodic obsessive compulsive disorder bipolar? A report of four cases.  J Affect Disord. 1999;  56 61-66
• 16 Zink M, Englisch S, Knopf U. et al . Augmentation of clozapine with valproic acid for clozapine-induced obsessive-compulsive symptoms.  Pharmacopsychiatry. 2007;  40 1-2
• 17 Zutshi A, Kamath P, Reddy YC. Bipolar and nonbipolar obsessive-compulsive disorder: a clinical exploration.  Compr Psychiat. 2007;  48 245-251