Agitated depression in substance dependence.

BACKGROUND Depression with psychomotor agitation (PMA; "agitated depression") is a putative psychiatric phenotype that appears to associate with some forms of substance dependence. However, it is unclear whether such relationships extend across different substances and independent (I-MDE) versus substance-induced (SI-MDE) subtypes of major depressive episodes. METHOD We examined whether lifetime depression with (vs. without) PMA was associated with lifetime substance dependence across individuals with lifetime: (1) I-MDE only (n=575); and (2) SI-MDE only (n=1683). Data were pooled from several family and genetic studies of substance dependence in which participants received identical structured interviews to diagnose DSM-IV mental disorders. RESULTS In I-MDE, PMA was significantly associated with alcohol, cocaine, opioid, other drug (hallucinogen, inhalant, speed-ball), and sedative dependence. After controlling for demographic and clinical co-factors, PMA's relationship to dependence on opioids, other drugs, and sedatives remained significant, but not its relationship to alcohol or cocaine. In SI-MDE, PMA was significantly associated with alcohol, cocaine, opioid, and other drug dependence. After adjusting for co-factors, associations remained significant for dependence on cocaine and opioids, but not alcohol or other drugs. Relationships between PMA and opioid dependence were stronger in I-MDE than SI-MDE. Depression subtype (I-MDE vs. SI-MDE) did not moderate relations between PMA and non-opioid forms of substance dependence. CONCLUSIONS Agitated depression associates with certain forms of substance dependence, particularly opioid dependence. MDE subtype did not alter most PMA-dependence associations, which suggests that the mechanisms underlying this comorbidity are complex and potentially bidirectional.