Predictors of switching from mania to depression in a large observational study across Europe (EMBLEM).
BACKGROUND
The risk of switching from mania to depression in bipolar disorder has been poorly studied. Large observational studies may be useful in identifying variables that predict switch to depression after mania and provide data on medication use and outcomes in "real world" patients.


METHODS
EMBLEM (European Mania in Bipolar Longitudinal Evaluation of Medication) is a 2-year, prospective, observational study of patients with a manic/mixed episode. Symptom severity measures included Clinical Global Impression-Bipolar Disorder scale (CGI-BP), Young Mania Rating Scale (YMRS) and 5-item Hamilton Depression Rating Scale. Switching was defined using CGI-BP mania and depression such that patients changed from manic and not depressed to depressed but not manic over two consecutive observations within the first 12 weeks of follow-up. Cox proportional hazards models identified baseline variables independently associated with switch to depression.


RESULTS
Of 2390 patients who participated in the maintenance phase (i.e. up to 24 months), 120 (5.0%) switched to depression within the first 12 weeks. Factors associated with greater switching to depression include previous depressive episodes, substance abuse, greater CGI-BP overall severity and benzodiazepine use. Factors associated with lower switching rates were greater CGI-BP depression, lower YMRS severity and atypical antipsychotic use.


CONCLUSIONS
The definition of switching biased against patients with mixed episodes being likely to switch.


CONCLUSIONS
Strictly defined, switch to depression from mania occurs in a small proportion of bipolar patients. Clinical history, illness severity, co-morbidities and treatment patterns are associated with switching to depression. Atypical antipsychotics may protect against switch to depression.
Vieta
Eduard
E
Department of Psychiatry, Hospital Clinic, University of Barcelona IDIBAPS, CIBER-SAM, Barcelona, Spain. evieta@clinic.ub.es
Angst
Jules
J
Reed
Catherine
C
Bertsch
Jordan
J
Haro
Josep Maria
JM
D000328:Adult; D000339:Affect; D000927:Anticonvulsants / Q000009:adverse effects / Q000627:therapeutic use; D000928:Antidepressive Agents / Q000009:adverse effects / Q000627:therapeutic use; D018692:Antimanic Agents / Q000009:adverse effects / Q000627:therapeutic use; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000627:therapeutic use; D001569:Benzodiazepines / Q000009:adverse effects / Q000627:therapeutic use; D001714:Bipolar Disorder / Q000175:diagnosis* / Q000188:drug therapy / Q000453:epidemiology / Q000523:psychology; D003430:Cross-Sectional Studies; D004359:Drug Therapy, Combination; D005060:Europe; D005260:Female; D006801:Humans; D006993:Hypnotics and Sedatives / Q000009:adverse effects / Q000627:therapeutic use; D016651:Lithium Carbonate / Q000009:adverse effects / Q000627:therapeutic use; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D011446:Prospective Studies; D011569:Psychiatric Status Rating Scales; D012306:Risk; D016896:Treatment Outcome; D055815:Young Adult
D000927:Anticonvulsants; D000928:Antidepressive Agents; D018692:Antimanic Agents; D014150:Antipsychotic Agents; D006993:Hypnotics and Sedatives; D001569:Benzodiazepines; D016651:Lithium Carbonate