Benedicto Parker

Olanzapine for schizophrenia refractory to typical and atypical antipsychotics: an open-label, prospective trial.

The role of olanzapine in treatment-resistant schizophrenia is still unresolved. This article presents an open-label, prospective, 14-week trial with olanzapine in patients with schizophrenia and schizoaffective disorder selected for unambiguous resistance to either clozapine or risperidone and to typical antipsychotics. Forty-three inpatients (mean age, 41.6 years; mean duration of illness, 21.7 years) were enrolled and treated after cross-titration from their previous antipsychotic treatment with olanzapine 10 to 40 mg daily without any concomitant antipsychotic medication. Patients were evaluated with the Positive and Negative Syndrome Scale (PANSS), the Clinical Global Impressions Scale, and the Extrapyramidal Symptom Rating Scale. The change with olanzapine treatment was associated with a PANSS total score improvement of 3.7 (SD = 15.6; not significant). There was a significant improvement for the PANSS cognitive and depression/anxiety factors, whereas the PANSS excitement factor worsened. The improvement rate was superior in patients receiving olanzapine doses higher than 20 mg. A total of 16.7% of patients reached response criteria set forth by a previous study. There was a significant decrease in extrapyramidal side effects (t = 2.04;p < 0.05) and statistically significant, yet modest, weight gain. These results indicate that olanzapine is only modestly effective in these severely treatment-resistant patients with schizophrenia. However, a trial with olanzapine can be recommended in these patients before moving to augmentation strategies, given the lack of proven alternatives and the observation that 16.7% of patients reached the response criteria.

Does social cognition training augment response to computer-assisted cognitive remediation for schizophrenia?

OBJECTIVES Cognitive remediation therapy (CRT) has shown significant improvement in cognition in schizophrenia. However, effect sizes of CRT have been reported to be modest raising the issue how to augment the effects of CRT on neurocognition and social cognition. Our aim was to examine whether the addition of computerized social cognition training would enhance the effects on neurocognition and social cognition as compared to CRT alone. METHODS This is a 12-week, parallel group trial of 131 in- and out-patients with schizophrenia randomized to CRT (COGPACK or Brain Fitness) with computerized social cognition training (MRIGE), or CRT alone for 36 sessions. Participants were assessed at baseline and after 12 weeks of treatment. Assessments included neurocognition, social cognition, psychopathology, and functioning. RESULTS The combined intervention, CRT + MRIGE, showed greater improvements in the MCCB indices of Visual Learning, Working Memory, Reasoning and Problem-Solving, and the neurocognitive composite score compared to CRT alone (Bonferroni adjusted p = 0.004, p = 0.005, p = 0.01, respectively), as did social cognition measures (Bonferroni adjusted p = 0.006, p = 0.005, respectively). CONCLUSIONS Supplementing CRT with computerized social cognition training produced greater benefits in neurocognition, including visual learning, memory, executive functions, and social cognition relative to cognitive training alone. These findings favoring the combined training may be contributed to both the greater overall amount of cognitive practice, as well as the specific cognitive functions engaged by the social cognition training.

T43. TRANSCRANIAL DIRECT-CURRENT STIMULATION (TDCS) IN PATIENTS WITH ULTRA-TREATMENT-REFRACTORY AUDITORY HALLUCINATIONS

Abstract Background Transcranial direct-current stimulation (tDCS), a noninvasive neurostimulation treatment, has been reported to show improvements in treatment-resistant auditory hallucinations in patients with schizophrenia. tDCS administered over a limited number of sessions effectively produced lasting attenuation of auditory hallucinations in otherwise stable outpatients. It has also been shown that tDCS may be a useful intervention for ameliorating cognitive deficits in patients with chronic schizophrenia. The purpose of this study was to test tDCS for auditory hallucinations in ultra-treatment resistant schizophrenia to assess if this form of neurostimulation can alleviate treatment-refractory auditory hallucination symptoms up to 4 weeks after the final treatment. In addition, we also wanted to examine the effects of tDCS on cognitive functions. Methods 28 inpatients with DSM-V schizophrenia and long-standing treatment resistance and persistent auditory verbal hallucinations were recruited. Each individual participated in behavioral assessments at baseline, endpoint and follow-up [PANSS and Auditory Hallucinations Rating Scale (AHRS) and MCCB cognitive battery] and were randomized to receive active vs. sham tDCS treatments. For active treatment, patients had the inhibitory (cathodal) tDCS electrode placed over left auditory cortex relative to an excitatory (anodal) electrode placed over frontal cortex on the right side. tDCS treatments took place for 20 min twice daily for 5 consecutive days. Assessment batteries were repeated following the 4 weeks of treatment. The Chattanooga, dual channel CHA-1335 stimulator with two 7 × 5 cm (35 cm2) sponge electrodes soaked in a saline solution (0.9% NaCl) was used for the delivery of 2 mA current. Results A total of 28 subjects were enrolled (tDCS, n = 13; Control, n = 15). 20 subjects completed the trial. 3 subjects dropped out of the active tDCS treatment group, while 4 subjects did not complete the control treatment due to early discharge from the hospital. Most subjects were male (tDCS n = 10, 76.9%; Control n = 6, 40.0%). Length of present psychiatric admission ranged from 1–25 months, with a mode of 2 months (n = 12) and average of 2.9 months. Participating inpatients were on clozapine, haloperidol, paliperidone depot, fluphenazine decanoate, paliperidone, olanzapine, and risperidone as primary medications. Repeated Measures ANOVA showed a significant difference for the auditory hallucination total score, frequency and number of voices over time (p < 0.05) with greater reduction in scores observed for the tDCS group. Improvements were maintained after 4 weeks. There was no significant change over time observed for the PANSS positive symptoms or total score, or for the PANSS Hallucinatory Behavior item score. When assessing cognitive functioning, only Working Memory change was significant (p = 0.048) between the tDCS and the Control group with the tDCS group showing significant improvement in T-Score as compared to the Control group. Discussion Subjects who received tDCS treatment showed a significant reduction in the frequency, number of voices, and total scores of their auditory hallucination. Additionally, subjects in the tDCS group showed significant improvement in the Working Memory. Our results indicate that patients who have been ultra-resistant to antipsychotic treatments and who received tDCS treatment presented with robust diminution of their auditory hallucinations. We conclude that tDCS seems to be effective not only for ambulatory, higher functioning patients, but also for much lower functioning patients with medication-refractory auditory verbal hallucinations.

Transcranial Direct-Current Stimulation in Ultra-Treatment-Resistant Schizophrenia

BACKGROUND Transcranial direct-current stimulation (tDCS), a non-invasive neurostimulation treatment, has been reported in a number of sham-controlled studies to show significant improvements in treatment-resistant auditory hallucinations in schizophrenia patients, primarily in ambulatory and higher-functioning patients, but little is known of the effects of tDCS on hospitalized, low-functioning inpatients. OBJECTIVE/HYPOTHESIS The purpose of this study was to examine the efficacy and safety of tDCS for auditory hallucinations in hospitalized ultra-treatment-resistant schizophrenia (TRS) and to evaluate the effects of tDCS on cognitive functions. We hypothesized that treatment non-response reported in previous tDCS studies may have been due to the insufficient duration of direct-current stimulation. METHODS Inpatient participants with DSM-V schizophrenia, long-standing treatment-resistance, and auditory verbal hallucinations (AVH) participated in this 4-week sham-controlled, randomized trial. Assessments included the Positive and Negative Syndrome Scale (PANSS) and MATRICS Consensus Cognitive Battery (MCCB) at baseline and endpoint (at the end of Week 4), and the Auditory Hallucinations Rating Scale (AHRS) administered at baseline, endpoint, and weekly throughout the study. Participants were randomized to receive active vs. sham tDCS treatments twice daily for 4 weeks. RESULTS Twenty-eight participants were enrolled (tDCS, n = 15; control, n = 13) and 21 participants completed all 4 weeks of the trial. Results showed a significant reduction for the auditory hallucination total score (p ≤ 0.05). We found a 21.9% decrease in AHRS Total Score for the tDCS group and a 12.6% decrease in AHRS Total Score for the control group. Significant reductions in frequency, number of voices over time, length of auditory hallucinations, and overall psychopathology were also observed for the tDCS group. When assessing cognitive functioning, only Working Memory showed improvement for the tDCS group. CONCLUSION Although there was only a small improvement noted in auditory hallucination scores for the tDCS group, this improvement was meaningful when compared to no standard treatment of the control group. While this makes the interpretation of clinical significance debatable, it does confirm that tDCS combined with pharmacological intervention can provide clinical gains over pharmacological intervention alone. Therefore, tDCS treatment appears to be effective not only for ambulatory, higher-functioning patients, but also for patients with ultra-treatment-resistant schizophrenia.