Mendel Fux

Double-blind, controlled, crossover trial of inositol versus fluvoxamine for the treatment of panic disorder.

Only 70% of patients respond to current treatments for panic disorder, and many discontinue drugs because of side effects. myo-Inositol, a natural isomer of glucose and a precursor for the second-messenger phosphatidyl-inositol system, has previously been found superior to placebo in the treatment of depression, panic disorder, and obsessive-compulsive disorder (OCD), but a direct comparison with an established drug has never been performed. A double-blind, controlled, random-order crossover study was undertaken to compare the effect of inositol with that of fluvoxamine in panic disorder. Twenty patients completed 1 month of inositol up to 18 g/day and 1 month of fluvoxamine up to 150 mg/day. Improvements on Hamilton Rating Scale for Anxiety scores, agoraphobia scores, and Clinical Global Impressions Scale scores were similar for both treatments. In the first month, inositol reduced the number of panic attacks per week (mean and SD) by 4.0 (2) compared with a reduction of 2.4 (2) with fluvoxamine (p = 0.049). Nausea and tiredness were more common with fluvoxamine (p = 0.02 and p = 0.01, respectively). Because inositol is a natural compound with few known side effects, it is attractive to patients who are ambivalent about taking psychiatric medication. Continuing reports of inositol’s efficacy in the treatment of depression, panic disorder, and OCD should stimulate replication studies.

A placebo-controlled cross-over trial of adjunctive EPA in OCD

Several clinical studies showed beneficial effects of omega-3 fatty acids in major affective disorders, including resistant depression. Some antidepressants are also effective, albeit less so, in obsessive-compulsive disorder (OCD). We therefore undertook a preliminary placebo-controlled cross-over trial of adjunctive eicosapentaenoic acid (EPA) in OCD. Eleven patients with current obsessive-compulsive disorder, who were on a stable maximally tolerated dose of SSRI with no further improvement over at least the last two months, were recruited. Subjects were randomly allocated to begin 6 weeks of placebo (2 g liquid paraffin per day) followed by 6 weeks of 2 g of EPA or EPA followed by placebo. Patients continued their prior SSRIs at the same dose. Assessments were performed with the Yale-Brown Obsessive-Compulsive Scale (YBOCS), and the Hamilton Rating Scales for depression (HAM-D) and anxiety (HAM-A). There were no effects of order of treatment. Time had a main effect of YBOCS scores; mean scores declined from 26.0 (+/-5) to 17.6 (+/-6) by week 6 on placebo and to 18.5 (+/-4) on EPA. There were no effects on HAM-D and HAM-A. No clinically relevant side effects were reported. The results of this study suggest that adjunctive EPA is ineffective against OCD.

Inositol versus placebo augmentation of serotonin reuptake inhibitors in the treatment of obsessive-compulsive disorder: a double-blind cross-over study.

Current serotonin reuptake inhibitor (SRI) treatments for obsessive-compulsive disorder (OCD) provide only partial benefit. A previous study suggested that inositol alone is efficacious in OCD. Ten DSM-IV OCD patients completed a study of 18 g inositol or placebo for 6 wk each in addition to ongoing SRI treatment in a double-blind randomized cross-over design. Weekly assessments included the Yale-Brown Obsessive-Compulsive Scale (YBOCS) and Hamilton Depression and Anxiety scales. No significant difference was found between the two treatment phases.

Realism of confidence in obsessive-compulsive checkers.

The study examined whether obsessive-compulsive (OC) checkers have reduced confidence in their knowledge. OC checkers were compared with panic disorder (PD) patients and nonpatient controls using a calibration-of-knowledge procedure. Participants completed a general knowledge questionnaire, rated their confidence in each answer, and estimated the total number of correct answers. These responses were converted to 2 measures of confidence relative to performance--over/underconfidence and over/underestimation. OC checkers had lower scores than nonpatients did on both measures, whereas the PD patients did not differ from either group. For the OC checkers, relative confidence was inversely related to the severity of obsessions. The authors speculate that confidence may depend on a confirmation bias in testing hypotheses and that the reduced confidence in OC checkers may reflect a disconfirmation bias in this population.

A double-blind crossover comparison of clomipramine and desipramine in the treatment of panic disorder

OBJECTIVE To compare the efficacy of clomipramine hydrochloride (CMI), a serotonin reuptake inhibitor with the noradrenergic tricyclic antidepressant agent, and desipramine hydrochloride (DMI) for patients with panic disorder (PD). METHOD Following a 2-week, single-blind placebo washout phase, 17 PD outpatients completed a 16-week, double-blind, crossover comparison of CMI and DMI. Key outcome measures included panic attacks frequency, the NIMH Global Scales for Anxiety, Depression and Impairment, Hamilton Anxiety Scale (Psychic and Somatic Subscales), Zung Anxiety Inventory (Raw and Index Subscales) and the Spielberger State Anxiety Scale. RESULTS Both CMI and DMI led to significant improvement from baseline placebo state in panic attacks frequency and behavioral ratings (p<0.001). CMI led to a greater reduction in the frequency of panic attacks (p=0.028) and was superior to DMI on ratings of anxiety: NIMH Global Anxiety, Zung Anxiety Scale (Raw and Index) and the Spielberger Anxiety Scale. No difference was found between the drugs on the NIMH Global Impairment Scale and the Hamilton Somatic and Psychic Scales. CONCLUSION Both drugs appeared to have significant therapeutic effects in patients with PD, but CMI appeared to be more effective. The effectiveness of the serotonergic drug suggests that the role of the serotonergic system in the pathogenesis of PD should be further explored.

Emergence of depressive symptoms during treatment for panic disorder with specific 5-hydroxytryptophan reuptake inhibitors

Selective serotonin reuptake inhibitors (SSRI) have been established as effective drugs in the treatment of depressive and anxiety disorders. However, there are also reports that they can induce depressive symptoms and suicidal thoughts in patients. Eighty of 230 patients who met the DSM‐III‐R criteria for panic disorder received, during the course of treatment, fluvoxamine (a selective serotonin reuptake inhibitor) at a dose level between 50–200 mg/day. The patients were clinically evaluated for a history of affective disorder and for the presence of affective symptoms before the treatment and for emergence of depressive symptoms during the treatment. Seven of the 80 patients (9%) developed symptoms of depression despite a good antianxiety response. Five of the 7 patients received fluvoxamine as second choice after tricyclic antidepressants (TCA). These patients had no history of affective disorder, and no symptoms of depression were present before the treatment with fluvoxamine. The depressive symptoms abated after the fluvoxamine was discontinued and TCA or clonazepam was prescribed. The depressive symptoms reappeared when fluoxetine was administered. None of these 7 patients developed depressive symptoms while treated with TCA or clonazepam. Among the 150 patients treated with TCA and benzodiazepines, not a single case of depression was seen in patients without a previous history of depression. These results suggest a vulnerability among some of panic disorder patients to noradrenergic‐serotonergic imbalance caused by SSRI, which has to be taken into clinical consideration.