Efficacy of bilateral repetitive transcranial magnetic stimulation for negative symptoms of schizophrenia: results of a multicenter double-blind randomized controlled trial.

BACKGROUND: Few studies have investigated the efficacy of repetitive transcranial magnetic stimulation (rTMS) treatment for negative symptoms of schizophrenia, reporting inconsistent results. We aimed to investigate whether 10 Hz stimulation of the bilateral dorsolateral prefrontal cortex during 3 weeks enhances treatment effects. METHOD: A multicenter double-blind randomized controlled trial was performed in 32 patients with schizophrenia or schizo-affective disorder, and moderate to severe negative symptoms [Positive and Negative Syndrome Scale (PANSS) negative subscale ⩾15]. Patients were randomized to a 3-week course of active or sham rTMS. Primary outcome was severity of negative symptoms as measured with the Scale for the Assessment of Negative Symptoms (SANS) and the PANSS negative symptom score. Secondary outcome measures included cognition, insight, quality of life and mood. Subjects were followed up at 4 weeks and at 3 months. For analysis of the data a mixed-effects linear model was used. RESULTS: A significant improvement of the SANS in the active group compared with sham up to 3 months follow-up (p = 0.03) was found. The PANSS negative symptom scores did not show a significant change (p = 0.19). Of the cognitive tests, only one showed a significant improvement after rTMS as compared with sham. Finally, a significant change of insight was found with better scores in the treatment group. CONCLUSIONS: Bilateral 10 Hz prefrontal rTMS reduced negative symptoms, as measured with the SANS. More studies are needed to investigate optimal parameters for rTMS, the cognitive effects and the neural basis.

Prediction of the antidepressant response to total sleep deprivation of depressed patients: longitudinal versus single day assessment of diurnal mood variation.

The relationship between diurnal variation of mood and the clinical response to total sleep deprivation (TSD) was investigated in 43 depressed patients. The question asked was whether the propensity to produce diurnal variations of mood or the actual mood course on the day before TSD determines the clinical response to TSD. Patients rated their mood three times daily during an experimental period of 56 days. The frequency as well as the amplitude of daily mood changes were assessed during this period. For each patient six TSDs were scheduled: two after days with a positive mood course, two after a negative mood course, and two after days without a diurnal change of mood. This strategy allowed comparisons of TSD responses within patients. Moreover, longitudinally and retrospectively assessed diurnal variation were compared with each other. It was found that patients vary largely in the occurrence of diurnal variations of mood. The propensity to produce diurnal variations either in terms of frequency or amplitude was positively correlated with the response to TSD. Within patients no differences were found in responses to TSDs applied after days with diurnal variations (positive or negative) or without diurnal variations. A second aim was to get more insight into the mechanism relating diurnal variations of mood and the TSD response. Therefore, the interrelatedness of various measures of diurnal variations, such as amplitudes and frequencies of positive or negative diurnal mood changes, was studied, as well as the relationships of these variables with TSD responses. On the basis of the strong interrelatedness it is suggested that they all reflect the same underlying mechanism, to be symbolized by an oscillator, producing positive daily fluctuations of mood.

A longitudinal study of diurnal mood variation in depression; characteristics and significance.

The course of 39 depressed in-patients' daily mood was recorded by means of frequent self-ratings during their entire stay (in total 3718 days). The frequency of diurnal variations largely varies between subjects without clear dichotomy in 'diurnal' and 'non-diurnal' subjects and the occurrence of diurnal variations is rather irregular. Mood variability measures rather than average daily mood improvement correlate with the response to sleep deprivation. These observations do not support theories of chronobiological rhythm disturbances in depression. It is argued that depressed subjects largely vary in susceptibility to stimuli. Signals generated by the biological clock or by processes related to the sleep-wake cycle are considered examples of such stimuli.

Prediction of the antidepressant response to total sleep deprivation by diurnal variation of mood.

The relationship between diurnal variation of mood and response to total sleep deprivation (TSD) was investigated in 131 depressed patients. This response was related to (1) the diurnal variation on the day before TSD as assessed by self-ratings of mood, and (2) the propensity to produce diurnal variations (the "diurnality") as assessed by the Hamilton Rating Scale for Depression. Three types of diurnality are distinguished: morning type (the propensity to feel better in the morning), evening type (the propensity to feel better in the evening), and a nondiurnal type. The results show that diurnality does predict the mood response to TSD. The direction of diurnality is decisive: patients who have the propensity to feel better in the evening benefit more from TSD than other patients.