The use of stimulants in depression: Results from a self-controlled register study.

Abstract

To investigate the effectiveness of stimulants in patients with depression, by using naturalistic outcome measures, such as psychiatric admissions, psychiatric bed-days and incidents of intentional self-harm or suicide attempts. Via linkage of the Danish nationwide health registers, we identified all patients with a diagnosis of depression initiating stimulants, including methylphenidate, modafinil, amphetamine, dexamphetamine or lisdexamphetamine, from 1995 to 2012. We used a mirror-image model to test whether redemption of a stimulant prescription was associated with a reduction in psychiatric admissions, inpatient days and incidents of intentional self-harm or suicide attempts. Specifically, the number of these outcomes in the 2 years leading up to redemption of a stimulant prescription was compared to the two subsequent years. Similar outcomes were used in a reverse mirror-image model to investigate the effect of stimulant termination. A total of 3354, 935 and 105 patients diagnosed with depression redeemed prescriptions for methylphenidate, modafinil or amphetamine/dexamphetamine/lisdexamphetamine, respectively. Initiation of methylphenidate was not associated with a significant change in psychiatric admissions (mean: -0.02 admissions, p = 0.11) or inpatient days (mean: 0.13 days, p = 0.74). Similar findings were made for modafinil and the amphetamines. In addition, no clinically relevant change in psychiatric admissions or inpatient days was found after termination of a stimulant. After initiation of methylphenidate, the incidents of self-harm or suicide attempts were reduced by 54%, from 68 to 31 events (p = 0.004). No significant change in incidents of self-harm or suicide attempts were found for modafinil or the amphetamines. This nationwide study, using naturalistic outcomes, does not support the use of stimulants in patients with depression. However, the use of methylphenidate was associated with a 54% reduction in incidents of self-harm or suicide attempts, indicating that methylphenidate may potentially be useful in patients with depression with suicidal- or self-harming behaviour. However, further studies are needed, before any firm conclusions can be made.