Lamotrigine plus quetiapine combination therapy in treatment-resistant bipolar depression

UMMS Affiliation

Department of Psychiatry

Publication Date


Document Type



Adult; Affect; Antimanic Agents; Antipsychotic Agents; *Bipolar Disorder; Diagnostic and Statistical Manual of Mental Disorders; *Dibenzothiazepines; *Drug Resistance; Drug Therapy, Combination; Female; Humans; Interview, Psychological; Male; Middle Aged; Monitoring, Physiologic; Pilot Projects; Psychiatric Status Rating Scales; Severity of Illness Index; Treatment Outcome; *Triazines; Xerostomia


Mental and Social Health | Psychiatry | Psychiatry and Psychology


BACKGROUND: Lamotrigine and quetiapine are commonly used in bipolar disorder, but there are no published systematic studies of their use in combination for treatment-resistant bipolar depression.

METHODS: We studied 39 trials in outpatients (15 with bipolar I disorder, 22 with bipolar II disorder, and 1 with bipolar disorder not otherwise specified; 1 patient had 2 trials) with depression resistant to quetiapine or lamotrigine who were taking a mean of 1.7 other prescription psychotropic medications. Patients were given either open-label lamotrigine or quetiapine naturalistically, for up to 12 weeks of combination therapy.

RESULTS: Lamotrigine (mean dose, 204.2 mg/d) plus quetiapine (mean dose, 188.5 mg/d) increased the euthymia rate (0.0% to 46.2%), decreased syndromal (79.5% to 30.8%) and subsyndromal (20.5% to 15.4%) depression rates, and improved Clinical Global Impression-Severity (mean change, -1.0) and Global Assessment of Functioning (mean change, +5.9) scores. Approximately one-fifth of patients discontinued therapy (20.5%) or required subsequent additional pharmacotherapy (20.5%). Only 10.3% discontinued due to adverse effects, and there was no significant change in mean body weight.

CONCLUSIONS: The findings of this uncontrolled open pilot study must be viewed with caution. However, randomized, double-blind, placebo-controlled studies are warranted to confirm the possibility that combination therapy with lamotrigine and quetiapine is effective and well tolerated in patients with treatment-resistant bipolar depression.


Ann Clin Psychiatry. 2011 Feb;23(1):17-24.

Journal/Book/Conference Title

Annals of clinical psychiatry : official journal of the American Academy of Clinical Psychiatrists

Related Resources

Link to Article in PubMed

PubMed ID