title: Effects of atypical antipsychotics on neurocognition in euthymic bipolar patients.
abstract: BACKGROUND
  Different factors may influence cognitive functioning in bipolar disorder such as the effect of subsyndromal symptoms, the history of psychotic symptomatology or substance abuse, negative symptomatology, chronicity, sleep disturbances, and hormonal factors. The effect of pharmacologic treatment on cognition is still uncertain because of an insufficient number of studies examining this issue.
  
  
  OBJECTIVE
  The aims of this study were to compare neuropsychologic performance of treated bipolar patients with that of controls, including unmedicated patients and healthy subjects, as well as to evaluate possible neurocognitive differences among 3 different atypical antipsychotics.
  
  
  METHODS
  A total of 119 subjects were included in the study. Of 79 Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition euthymic bipolar patients, 68 were treated with one atypical antipsychotic, quetiapine (n = 12), olanzapine (n = 26), or risperidone (n = 30). Sixteen patients were drug-free. The 4 groups were compared with a sample of drug-naïve patients and a healthy control group (n = 35) on several clinical and neuropsychologic variables, especially on the domains of attention, verbal memory, and executive functions. Euthymia was defined by a score of 6 or less at the Young Mania Rating Scale and a score of 8 or less at the Hamilton Depression Rating Scale for at least 6 months.
  
  
  RESULTS
  The 5 groups did not differ in age, years of education, sex distribution, or estimated premorbid IQ. The 4 patients groups did not differ in chronicity, age of onset, total number of episodes, and number of hospitalizations. No differences were found regarding antipsychotic dosages between the groups. Bipolar patients performed poorly on most neuropsychologic measures as compared with healthy controls. After controlling for Hamilton Depression Rating Scale symptoms, no significant change in the results was observed. Because many patients with antipsychotic treatment had a history of psychotic symptoms, we performed multivariate analysis of covariance controlling for this variable. Bipolar patients taking 1 of the 3 antipsychotics presented with dose-independent significant deficits in most cognitive tasks compared with healthy controls. After several head-to-head group comparisons, the patients receiving quetiapine showed a better performance in learning task, short-term memory, and recognition task assessed with the California Verbal Learning Test and verbal fluency (P < .05).
  
  
  CONCLUSIONS
  Our results confirm the findings of previous studies of cognitive deficits in bipolar disorder. Untreated euthymic patients showed better cognitive performance than did patients on atypical antipsychotics. Some iatrogenic-pharmacologic effect, therefore, cannot be excluded, but quetiapine seemed to be less associated with impairment in measures of verbal memory than olanzapine or risperidone. We suggest to use drugs in bipolar disorder with a lower risk of cognitive adverse effects. However, randomized controlled trials are urgently needed to give a definite answer to this critical problem.
authors.affiliation: Bipolar Disorders Program, Clinical Institute of Neuroscience, University Hospital Clinic, IDIBAPS, CIBERSAM, University of Barcelona, Barcelona, Catalonia, Spain.
authors.forename: Carla
authors.initials: C
authors.lastname: Torrent
authors.forename: Anabel
authors.initials: A
authors.lastname: Martinez-Arán
authors.forename: Claire
authors.initials: C
authors.lastname: Daban
authors.forename: Benedikt
authors.initials: B
authors.lastname: Amann
authors.forename: Vicente
authors.initials: V
authors.lastname: Balanzá-Martínez
authors.forename: Caterina
authors.initials: C
authors.lastname: del Mar Bonnín
authors.forename: Núria
authors.initials: N
authors.lastname: Cruz
authors.forename: Carolina
authors.initials: C
authors.lastname: Franco
authors.forename: Rafael
authors.initials: R
authors.lastname: Tabarés-Seisdedos
authors.forename: Eduard
authors.initials: E
authors.lastname: Vieta
mesh_terms: D000293:Adolescent; D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D001288:Attention / Q000187:drug effects; D001569:Benzodiazepines / Q000627:therapeutic use; D001714:Bipolar Disorder / Q000188:drug therapy* / Q000523:psychology; D016022:Case-Control Studies; D003071:Cognition / Q000187:drug effects*; D003987:Dibenzothiazepines / Q000627:therapeutic use; D004644:Emotions / Q000187:drug effects; D056344:Executive Function / Q000187:drug effects; D005260:Female; D006801:Humans; D008297:Male; D008568:Memory / Q000187:drug effects; D008875:Middle Aged; D009483:Neuropsychological Tests; D000077152:Olanzapine; D011569:Psychiatric Status Rating Scales; D000069348:Quetiapine Fumarate; D018967:Risperidone / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D003987:Dibenzothiazepines; D001569:Benzodiazepines; D000069348:Quetiapine Fumarate; D018967:Risperidone; D000077152:Olanzapine