Risperidone augmentation in refractory obsessive-compulsive disorder: an open-label study.

Risperidone, an atypical neuroleptic, has been proposed for augmentation strategies in resistant obsessive-compulsive disorder (OCD). We report the results of an open-label trial on the use of the combination of serotonin reuptake inhibitors (SRIs) with risperidone in 20 refractory OCD outpatients. All patients had been suffering from OCD, according to DSM-IV criteria, for at least 2 years and had various comorbid disorders. All had been treated with a SRI at adequate dosages for at least 6 months, but had failed to respond. Therefore, risperidone was added and the dosage titrated up to the mean dose of 3 mg/day over 8 weeks. After 2 months of this regimen, all patients had shown a reduction in obsessive-compulsive symptoms, as assessed by the decrease in the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) total score, particularly those with a lifetime comorbidity with bipolar disorder; only three patients reported mild sedation and postural hypotension, two mild extrapyramidal side-effects (tremors and akatysia) and two an increased appetite. All these effects were well tolerated and no patient halted the treatment. The addition of risperidone would appear to be a useful strategy for augmenting SRI effectiveness in refractory OCD patients.

Depressive comorbidity of panic, social phobic, and obsessive-compulsive disorders re-examined: is there a bipolar II connection?

Utilizing the DSM-III-R schema, we have investigated lifetime comorbidity between panic disorder with or without agoraphobia (PD), social phobia (SP) and obsessive-compulsive disorder (OCD) on the one hand, and mood disorder on the other. Compared with PD, the results for SP and OCD showed significantly higher numbers of comorbid anxiety and mood disorders. In addition, SP and OCD were significantly more likely to cooccur with each other than with PD. The complexity of these comorbid patterns is underscored by the finding of significantly higher numbers of anxiety disorders in those with lifetime comorbidity with bipolar (especially bipolar II) disorder. We conclude that the comorbidity between anxiety and mood disorders - conventionally conceived as the relationship between anxiety and unipolar depressive states -- might very well extend into the domain of bipolar spectrum disorders in a subset of these disorders. Among the latter, the spontaneous or antidepressant-induced switches into brief disinhibited (hypomanic) behavior can be conceptualized to lie on a dimensional continuum with the temperamental inhibition (or constraint) underlying the anxiety disorders under discussion. These findings and theoretical considerations have important therapeutic implications.

Episodic course in obsessive-compulsive disorder.

The course of obsessive-compulsive disorder (OCD) is variable, ranging from episodic to chronic. We hypothesised that the former course is more likely to be related to bipolar mood disorders. With the use of a specially constructed OCD questionnaire, we studied 135 patients fulfilling DSM-III-R criteria for OCD with an illness duration of at least 10 years and divided by course: 27.4% were episodic and 72.6% chronic. We compared clinical and familial characteristics and comorbidity. Univariate analyses showed that episodic OCD had a significantly lower rate of checking rituals and a significantly higher rate of a positive family history for mood disorder. Multivariate stepwise discriminant analysis revealed a positive and significant relationship between episodic course, family history for mood disorders, lifetime comorbidity for panic and bipolar-II disorders, late age at onset and negative correlation with generalized anxiety disorder. These data suggest that the episodic course of OCD has important clinical correlates which are related to cyclic mood disorders. This correlation has implications for treatment and research strategies on the aetiology within a subpopulation of OCD.

The clinical impact of bipolar and unipolar affective comorbidity on obsessive-compulsive disorder.

Previous studies on the comorbidity of Obsessive-Compulsive Disorder (OCD) have largely focused on comorbidity with major depressive and anxiety disorders. The present investigation deals with a more complex pattern of comorbidity involving bipolarity. Indeed, in a consecutive series of 315 OCD outpatients, 15.7% had such comorbidity (mostly with bipolar II disorder). Unlike non-bipolar OCD patients, these had a more gradual onset of their OCD which, nonetheless, pursued a more episodic course with a greater number of concurrent major depressive episodes. These bipolar OCD patients had a significantly higher rate of sexual and religious obsessions, and a significantly lower rate of checking rituals. OCD probands with non-bipolar major depressive comorbidity (34.8%) were then compared with the remainder of OCD. These 'unipolar' OCD were older, had a more chronic course with hospitalizations and suicide attempts, had greater comorbidity with generalized anxiety disorder and caffeine abuse; finally, they were more likely to have aggressive obsessions and those with a philosophical, superstitious or bizarre content. Our data suggest that when comorbidity occurs with bipolar and unipolar affective disorders it has a differential impact on the clinical characteristics, comorbidity and course of OCD. We submit that the presence of major depression in OCD is incidental, as OCD in such cases dominates the course and dictates treatment choice. By contrast, when bipolar and obsessive-compulsive disorders co-exist, bipolarity should take precedence in diagnosis, course and treatment considerations.

A double-blind study of fluvoxamine and clomipramine in the treatment of obsessive-compulsive disorder.

A double-blind trial was carried out to assess the efficacy and safety of fluvoxamine, a selective serotonin reuptake inhibitor, in comparison with clomipramine, a classical tricyclic antidepressant, in the treatment of obsessive-compulsive disorder. A total of 26 individuals with obsessive-compulsive disorder and with no comorbid disorders at baseline were included in the study. The obsessive-compulsive disorder symptom severity was rated using the Yale-Brown Obsessive-Compulsive Scale and the Clinical Global Impression Scale. The primary efficacy measures indicated an equal improvement in the two groups (38% in the patients taking fluvoxamine and 40% in those taking clomipramine, as compared with baseline values), but onset was faster in the clomipramine group. Side effects, in particular anticholinergic side effects, were more prominent in the clomipramine group. The present double-blind trial confirms an equal efficacy of clomipramine and fluvoxamine in obsessive-compulsive patients. Although clomipramine had a faster onset, fluvoxamine was better tolerated, so that it seems more suitable for long-term treatment of obsessive-compulsive patients.

Changes in platelet markers of obsessive-compulsive patients during a double-blind trial of fluvoxamine versus clomipramine.

Abnormalities of platelet serotonin (5-HT) transporter, which are supposed to reflect similar dysfunctions in the central nervous system (CNS), have been reported in obsessive-compulsive disorder (OCD). Other platelet parameters altered in OCD are represented by phenolsulfotransferase (PST) activity, an enzyme involved in the catabolism of catecholic neuro-transmitters, and peripheral benzodiazepine receptors. Since no information is available on the behavior of these putative markers during antiobsessive treatments, the aim of the present study was to measure and compare 3H-imipramine (3H-IMI) binding, which labels the 5-HT transporter, PST activity, and 3H-PK 11,195 binding, which labels peripheral benzodiazepine receptors, in a group of 18 patients with obsessive-compulsive disorder (OCD) before and after a treatment with fluvoxamine versus clomipramine. The results showed that at baseline the patients had a decreased number of 3H-IMI binding sites, which correlated negatively with the Y-BOCS total score, an increased PST activity and no difference in 3H-PK 11,195 binding, as compared with healthy volunteers. After eight weeks of treatment with either clomipramine or fluvoxamine, which was effective in all patients, the number of 3H-IMI binding sites increased significantly toward normal values, while the PST showed no change. These findings suggest that the reduction in 3H-IMI binding sites in OCD may be related to the severity of the illness and possibly to a positive response to serotonin re-uptake inhibitors, and might be considered as a state-dependent marker, whereas the PST activity would seem to be a trait of the illness.

Decreased platelet 3H-paroxetine binding in obsessive-compulsive patients.

The similarities between the serotonin (5-HT) transporter in both human platelets and human brain permit us to investigate this structure in patients with different psychiatric disorders. Several reports have shown abnormalities of the 5-HT transporter, by means of the measurement of the 5-HT uptake or of the 3H-imipramine binding, in platelets of patients with obsessive-compulsive disorder (OCD). The availability of the ligand 3H-paroxetine, a selective 5-HT reuptake inhibitor, to label the 5-HT transporter, promoted us to evaluate the binding of 3H-paroxetine in platelets of 18 drug-free patients with OCD. The results, showing that the patients had a lower number of 3H-paroxetine sites, which is inversely correlated with the Yale Brown Obsessive-Compulsive Scale total score, than a similar group of controls, add supporting evidence to the involvement of 5-HT in OCD. In addition, the decreased functionality of the 5-HT transporter seems to be linked to the severity of OC symptoms.

Comorbidity in obsessive-compulsive disorder: focus on depression.

The authors investigated the comorbidity between obsessive-compulsive disorder (OCD) and other psychiatric disorders in a group of 154 outpatients. The influence of an associate major depressive disorder (MDD) on the outcome of treatment with clomipramine was examined in a subgroup of 52 patients. The results showed that MDD was the most frequent disorder associated with OCD (almost 20% of the patients), followed by generalized anxiety and panic disorder. The co-presence of depression delayed the effect of clomipramine.