BOCA RATON, FLA. — A combination of escitalopram and bupropion might produce early remission in as many as one-third of patients with unipolar depression, according to a pilot study presented at a meeting of the New Clinical Drug Evaluation Unit sponsored by the National Institute of Mental Health.
However, the faster onset of action and increased remission rate observed with this combination compared with monotherapy come at a cost of increased adverse events. “In my mind, the adverse events were manageable in most patients,” said Jonathan W. Stewart, M.D., a researcher with the depression evaluation service at Columbia University, New York.
Delays are inherent in a sequential monotherapy approach to antidepressant treatment. Mechanistic delays include the time it takes for biochemical effects to occur. Dosing delays occur as physicians wait for a patient to get better before increasing the dose. In addition, there are programmatic delays because “we wait to see if the first one does not work before we start the second drug,” he said.
Dr. Stewart assessed 29 outpatients with major depressive disorder. The mean age was 38 years, and the patients were moderately depressed at study entry. Exclusion criteria included a history of seizures, substance abuse/dependence, bipolar disorder, or current use of other psychoactive drugs.
“We decided to mix escitalopram [Lexapro] with bupropion [Wellbutrin]. This combination may address a mechanistic delay inherent in” treatment with selective serotonin reuptake inhibitors, Dr. Stewart said. He added that the use of two effective antidepressants might overcome programmatic delays.
There was a rapid dose escalation during the first 15 days, after which dosages were stabilized to day 56. Almost half of the patients, 49%, followed the protocol dosing, and 54% were on the maximum dosages at study completion at 8 weeks.
At 2 weeks, 10 of 29 patients (34%) met remission criteria—defined as a Hamilton Rating Scale for Depression (HAMD-17) score of less than 8. “So we're getting a third of the patients better at 2 weeks,” he noted. The mean score at 2 weeks was 11.
By comparison, there is a 6% remission rate with monotherapy at 2 weeks, according to Dr. Stewart's own unpublished data for more than 500 patients.
At 8 weeks, 18 patients (62%) met remission criteria, and the mean HAMD-17 score was 6. Dr. Stewart said that the remission rate with monotherapy in his own unpublished data is 38%.
A total of six patients withdrew from the study, four because of adverse events. The most common adverse events were sleep related (reported by 55% of participants), including daytime sedation and insomnia. A total of 38% reported gastrointestinal effects, including abdominal pain and constipation, and 24% reported sexual effects, including decreased libido and anorgasmia. Patients also reported word-finding difficulty, headaches, dizziness, hives, sweating, increased blood pressure, and dizziness.
Despite the early onset of action of an escitalopram (Lexapro) and bupropion combination, efficacy beyond 2 weeks looks similar to other combinations, Dr. Stewart said.