Joshua T Kantrowitz1, Pejman Sehatpour2, Michael Avissar3, Guillermo Horga3, Anna Gwak3, Mathew J Hoptman4, Odeta Beggel5, Ragy R Girgis3, Blair Vail3, Gail Silipo5, Marlene Carlson3, Daniel C Javitt2. 1. Schizophrenia Research Center, Nathan Kline Institute, Orangeburg, NY, 10962, USA; Division of Experimental Therapeutics, Department of Psychiatry, Columbia University, USA; Division of Experimental Therapeutics, Department of Psychiatry, New York State Psychiatric Institute, New York, NY, 10032, USA. Electronic address: jk3380@cumc.columbia.edu. 2. Schizophrenia Research Center, Nathan Kline Institute, Orangeburg, NY, 10962, USA; Division of Experimental Therapeutics, Department of Psychiatry, Columbia University, USA; Division of Experimental Therapeutics, Department of Psychiatry, New York State Psychiatric Institute, New York, NY, 10032, USA. 3. Division of Experimental Therapeutics, Department of Psychiatry, Columbia University, USA; Division of Experimental Therapeutics, Department of Psychiatry, New York State Psychiatric Institute, New York, NY, 10032, USA. 4. Schizophrenia Research Center, Nathan Kline Institute, Orangeburg, NY, 10962, USA; Department of Psychiatry, NYU School of Medicine, New York, NY, 10016, USA. 5. Schizophrenia Research Center, Nathan Kline Institute, Orangeburg, NY, 10962, USA.
Abstract
BACKGROUND:Transcranial direct current stimulation (tDCS) is a potentially novel treatment for antipsychotic-resistant auditory verbal hallucinations (AVH) in schizophrenia. Nevertheless, results have been mixed across studies. METHODS: 89 schizophrenia/schizoaffective subjects (active: 47; Sham: 42) were randomized to five days of twice-daily 20-min active tDCS vs. sham treatments across two recruitment sites. AVH severity was assessed using the Auditory Hallucination Rating Scale (AHRS) total score. To assess target engagement, MRI was obtained in a sub sample. RESULTS: We observed a statistically significant, moderate effect-size change in AHRS total score across one-week and one-month favoring active treatment following covariation for baseline symptoms and antipsychotic dose (p = 0.036; d = 0.48). Greatest change was observed on the AHRS loudness item (p = 0.003; d = 0.69). In exploratory analyses, greatest effects on AHRS were observed in patients with lower cognitive symptoms (d = 0.61). In target engagement analysis, suprathreshold mean field-strength (>0.2 V/m) was seen within language-sensitive regions. However, off-target field-strength, which correlated significantly with less robust clinical response, was observed in anterior regions. CONCLUSIONS: This is the largest study of tDCS for persistent AVH conducted to date. We replicate previous reports of significant therapeutic benefit, but only if medication dosage is considered, with patients receiving lowest medication dosage showing greatest effect. Response was also greatest in patients with lowest levels of cognitive symptoms. Overall, these findings support continued development of tDCS for persistent AVH, but also suggest that response may be influenced by specific patient and treatment characteristics. CLINICALTRIALS.GOV: NCT01898299.
RCT Entities:
BACKGROUND: Transcranial direct current stimulation (tDCS) is a potentially novel treatment for antipsychotic-resistant auditory verbal hallucinations (AVH) in schizophrenia. Nevertheless, results have been mixed across studies. METHODS: 89 schizophrenia/schizoaffective subjects (active: 47; Sham: 42) were randomized to five days of twice-daily 20-min active tDCS vs. sham treatments across two recruitment sites. AVH severity was assessed using the Auditory Hallucination Rating Scale (AHRS) total score. To assess target engagement, MRI was obtained in a sub sample. RESULTS: We observed a statistically significant, moderate effect-size change in AHRS total score across one-week and one-month favoring active treatment following covariation for baseline symptoms and antipsychotic dose (p = 0.036; d = 0.48). Greatest change was observed on the AHRS loudness item (p = 0.003; d = 0.69). In exploratory analyses, greatest effects on AHRS were observed in patients with lower cognitive symptoms (d = 0.61). In target engagement analysis, suprathreshold mean field-strength (>0.2 V/m) was seen within language-sensitive regions. However, off-target field-strength, which correlated significantly with less robust clinical response, was observed in anterior regions. CONCLUSIONS: This is the largest study of tDCS for persistent AVH conducted to date. We replicate previous reports of significant therapeutic benefit, but only if medication dosage is considered, with patients receiving lowest medication dosage showing greatest effect. Response was also greatest in patients with lowest levels of cognitive symptoms. Overall, these findings support continued development of tDCS for persistent AVH, but also suggest that response may be influenced by specific patient and treatment characteristics. CLINICALTRIALS.GOV: NCT01898299.
Authors: Leandro da Costa Lane Valiengo; Stephan Goerigk; Pedro Caldana Gordon; Frank Padberg; Mauricio Henriques Serpa; Stephanie Koebe; Leonardo Afonso Dos Santos; Roger Alberto Marcos Lovera; Juliana Barbosa de Carvalho; Martinus van de Bilt; Acioly L T Lacerda; Helio Elkis; Wagner Farid Gattaz; Andre R Brunoni Journal: JAMA Psychiatry Date: 2020-02-01 Impact factor: 21.596
Authors: Daniel C Javitt; Steven J Siegel; Kevin M Spencer; Daniel H Mathalon; L Elliot Hong; Antigona Martinez; Cindy L Ehlers; Atheir I Abbas; Tobias Teichert; Peter Lakatos; Thilo Womelsdorf Journal: Neuropsychopharmacology Date: 2020-05-06 Impact factor: 8.294
Authors: Clément Dondé; Antigona Martínez; Joshua T Kantrowitz; Gail Silipo; Elisa C Dias; Gaurav H Patel; Juan Sanchez-Peña; Cheryl M Corcoran; Alice Medalia; Alice Saperstein; Blair Vail; Daniel C Javitt Journal: Transl Psychiatry Date: 2019-09-06 Impact factor: 6.222