title: Superior chronic tolerability of adjunctive modafinil compared to pramipexole in treatment-resistant bipolar disorder.
abstract: BACKGROUND
  Suboptimal outcomes are common in bipolar disorder (BD) pharmacotherapy, and may be mitigated with novel adjunctive agents such as modafinil (a low-affinity dopamine transport inhibitor) and pramipexole (a dopamine D2/D3 receptor agonist). While uncontrolled long-term effectiveness data have been reported for these treatments, reports specifically assessing their comparative acute versus chronic tolerability in BD are lacking. Such information, particularly in relation to discontinuation causes, has substantial relevance, providing initial indications to clinicians which treatment may be better tolerated, and to researchers which agent ought to be assessed in longer-term controlled trials.
  
  
  METHODS
  BD outpatients assessed with the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) Affective Disorders Evaluation, and followed with the STEP-BD Clinical Monitoring Form, were naturalistically prescribed adjunctive modafinil or pramipexole, and somatic/psychiatric intolerability discontinuation rates were compared.
  
  
  RESULTS
  Among 63 BD outpatients (mean ± SD age 43.5 ± 14.3 years, 60.3% female, 42.9% type I, 44.4% type II, 12.7% type not otherwise specified), taking 3.5 ± 1.5 (median 3) concurrent prescription psychotropics, adjunctive modafinil (n=24) for 626.9 ± 863.9 (286) days versus pramipexole (n=39) for 473.7 ± 613.4 (214; p=0.51) days yielded a 26.0% lower somatic/psychiatric intolerability discontinuation rate (12.5% vs. 38.5%; p<0.05), with most of the difference accounted for by more pramipexole somatic intolerability discontinuations, due to nausea and sedation, after the first 12 weeks of treatment.
  
  
  CONCLUSIONS
  No placebo comparison group. Small sample of predominantly female Caucasian insured outpatients, taking complex concurrent medication regimens.
  
  
  CONCLUSIONS
  Further studies are warranted to assess our preliminary observation that modafinil, compared to pramipexole, may be better tolerated for longer-term BD treatment.
authors.affiliation: Department of Psychiatry, University of Milan, Fondazione IRCCS Ca'Granda, Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: Bernardo
authors.initials: B
authors.lastname: Dell'osso
authors.forename: Sara
authors.initials: S
authors.lastname: Timtim
authors.forename: Farnaz
authors.initials: F
authors.lastname: Hooshmand
authors.forename: Shefali
authors.initials: S
authors.lastname: Miller
authors.forename: Po W
authors.initials: PW
authors.lastname: Wang
authors.forename: Shelley J
authors.initials: SJ
authors.lastname: Hill
authors.forename: Natalie
authors.initials: N
authors.lastname: Portillo
authors.forename: Terence A
authors.initials: TA
authors.lastname: Ketter
mesh_terms: D000328:Adult; D001559:Benzhydryl Compounds / Q000627:therapeutic use*; D052160:Benzothiazoles / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000188:drug therapy*; D017024:Chemotherapy, Adjuvant; D004361:Drug Tolerance; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077408:Modafinil; D000077487:Pramipexole; D011619:Psychotropic Drugs / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D001559:Benzhydryl Compounds; D052160:Benzothiazoles; D011619:Psychotropic Drugs; D000077487:Pramipexole; D000077408:Modafinil