title: Comparing the effect of clozapine and risperidone on cue reactivity in male patients with schizophrenia and a cannabis use disorder: A randomized fMRI study.
abstract: Cannabis use disorders (CUDs) are highly comorbid in patients with schizophrenia and associated with poor outcome. Clozapine has been put forward as the first choice antipsychotic in this patient group. However, little is known about the mechanisms underlying the assumed superiority of clozapine.
  
  
  
  A total of 38 patients with DSM-IV schizophrenia (30 with and 8 without a DSM-IV CUD) and 20 healthy comparison subjects were included between April 2009 and June 2012. Patients were randomized to antipsychotic treatment with clozapine or risperidone. At baseline and after 4weeks of medication, brain response to cannabis-related, positive and neutral images was measured using functional MRI. Neural correlates of cue reactivity were assessed in the following regions of interest: amygdala, ventral striatum, insula, thalamus, orbitofrontal cortex and anterior cingulate cortex. Subjective craving was assessed using self-report questionnaires (OCDUS and MCQ).
  
  
  
  At baseline, patients with a comorbid CUD showed higher subjective craving and greater activation in response to cannabis-related images compared to patients without a CUD and healthy controls in most regions of interest. Clozapine treated patients reported a greater reduction in craving (F(1,28)=6.0, p=0.04) and showed a larger decrease in amygdala activation during cannabis-related images compared to risperidone treated patients (T=3.94, pFWE=0.006). In addition, significant correlations were found between subjective craving and thalamus and insula activation during cannabis-related images.
  
  
  
  These findings provide evidence that clozapine is superior to risperidone in decreasing subjective craving and cue reactivity for cannabis-related images probably due to a differential effect on dopaminergic neurotransmission.
  
  
  
  'Nederlands trial register' (http://www.trialregister.nl), nr NTR1761, http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=1761.
authors.affiliation: Department of Psychiatry, Academic Medical Centre, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. Electronic address: m.w.machielsen@amc.nl.
authors.forename: Marise W J
authors.initials: MWJ
authors.lastname: Machielsen
authors.affiliation: Department of Psychiatry, Academic Medical Centre, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands; Department of Psychiatry, VU University Medical Center, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands.
authors.forename: Dick J
authors.initials: DJ
authors.lastname: Veltman
authors.affiliation: Department of Psychiatry, Academic Medical Centre, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
authors.forename: Wim
authors.initials: W
authors.lastname: van den Brink
authors.affiliation: Department of Psychiatry, Academic Medical Centre, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
authors.forename: Lieuwe
authors.initials: L
authors.lastname: de Haan
mesh_terms: D014150:Antipsychotic Agents / Q000627:therapeutic use*; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000503:physiopathology; D001931:Brain Mapping; D003024:Clozapine / Q000627:therapeutic use*; D015897:Comorbidity; D066249:Craving / Q000187:drug effects / Q000502:physiology; D003463:Cues; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D002189:Marijuana Abuse / Q000150:complications* / Q000000981:diagnostic imaging / Q000503:physiopathology; D055118:Medication Adherence; D018967:Risperidone / Q000627:therapeutic use*; D012559:Schizophrenia / Q000150:complications / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology; D016896:Treatment Outcome; D014796:Visual Perception / Q000187:drug effects / Q000502:physiology; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D003024:Clozapine; D018967:Risperidone
keywords: Cannabis; Clozapine; Craving; Imaging; Risperidone; Schizophrenia