Stimulants for Depression

Despite the fact that stimulants like cocaine, amphetamines and methamphetamines are heavily abused drugs which often cause severe depression in users and former users (MacInnes, 2001 and others), some psychiatrists prescribe stimulants as a treatment for depression with very little research to support this practice. While depression is often a chronic illness requiring long-term treatment, no controlled study of stimulant treatment of depression exceeds 7 weeks and some are as short as eight days.  All but one have been very small in size.  The few studies comparing stimulants like methylphenidate to standard anti-depressants strongly suggest stimulants are inferior.

It is my opinion that at the present time, because of the serious abuse potential of stimulant medication and the huge number of alternatives available, it is wrong to use stimulants to treat depression in children or adults.  Perhaps, at some time in the future, higher quality research will find value for stimulants in the treatment of depression, but this remains to be seen.  It seems certain that stimulants should hardly ever be used in the treatment of depression and, if used, should be for very short durations.

Brief DB HIV Fatigue Methylphenidate and Pemoline: 109 adults completed a 6-week trial; the 15 patients (41%) receiving methylphenidate and 12 patients (36%) receiving pemoline demonstrated a clinically significant improvement in fatigue compared with 6 patients (15%) receiving placebo. Patients receiving methylphenidate or pemoline demonstrated significantly more improvement in fatigue on several self-reported rating scales. Arch Intern Med 2001 Feb 12;161(3):411-20.

Very Small Study Claims Methylphenidate Helped Elderly Depression as Adjunct: In a very small, 10-week DB PC study of 16 elderly outpatients with major depression, an accelerated response was observed by week 3 in five subjects receiving citalopram+methylphenidate and in none of those receiving citalopram alone. The combination patients also had more improvement in depressive symptoms. Methylphenidate-enhanced antidepressant response to citalopram in the elderly: a double-blind, placebo-controlled pilot trial. Lavretsky H, et al. UCLA. . Am J Geriatr Psychiatry 2006 Feb;14(2):181-5.

Very Brief DB Post-Stroke Rehab: Arch Phys Med Rehabil 1998 Sep;79(9):1047-50. This 21-patient DB PC study by a Univ. of Wisconsin psychiatrist in Milwaukee. Methylphenidate treatment scored lower on the HAM-D (F(1,18)=5.714, p=.028), lower on the ZDS (F(1,18)=4.206, p=.055), higher on the M-FIM (F(1,18)=5.374, p=.032), and higher on the FMS (motor functioning) (F(1,9)=4.060, p=.075) than patients receiving placebo.

Extremely Brief, Very Small DB Older Depressed: Am J Psychiatry 1995 Jun;152(6):929-31. 16 older, medically-ill in DB PC 8 days. Claims those treated with methylphenidate did better.

Methylphenidate = Desipramine in Small DB: 20 HIV positive with depression. DB Desipramine up to 150 mg and methylphenidate up to 30mg. No difference is speed or degree of benefit. Duration? Int J Psychiatry Med 1995;25(1):53-67.

Claims d-Amphetamine Responders Differ: Author claims that some patients respond to methylphenidate, others to d-amphetamine, but that many will not respond to both. He presents no controlled research to support his claims. J Clin Psychiatry 1993 Sep;54(9):349-55

Review Says Stimulants Inferior: The report reviews the 10 placebo-controlled studies of stimulant drugs in primary depression as of 1989, with one exception, indicated little advantage of stimulant drugs over placebo. The author says that anti-depressants such as imipramine are superior. He notes that there is the unresearched issue of habituation with stimulant medication. J Clin Psychiatry 1989 Jul;50(7):241-9

No Benefit Mild Depression in Small DB: 20 patients. Methylphenidate vs. placebo. HAM-D 14-24. J Clin Psychiatry 1985 Dec;46(12):525-7

Stimulant Abusers Say Stimulants Cause Severe Depression, Anxiety, Paranoia: Drug users (n = 158) were contacted and interviewed in non-clinical community settings about their use of Ecstasy, cocaine powder, and amphetamines and the adverse effects of these drugs. Subjects reported a wide range of adverse effects including anxiety problems, depression, mood swings, feelings of paranoia, and panic attacks. Sleep and appetite disturbances were the most commonly reported problems. About half of all subjects reported depression and paranoid feelings associated with their stimulant use. Many of those reporting problems stated that these were mild. However, for all drugs, a substantial minority of users reported adverse effects which they rated as 'severe'. Between 30 and 55% of the sample reported having had at least one 'severe' adverse effect (30% cocaine, 35% Ecstasy and 55% amphetamine). Drug Alcohol Depend 1997 Mar 14;44(2-3):87-94. Maudsley National Addiction Center in London, Adverse effects of stimulant drugs in a community sample of drug users. Williamson S, Gossop M, Powis B, Griffiths P, Fountain J, Strang J.

Depression Very Common in Amphetamine Abusers: Interview of 301 abusers. The most commonly reported symptoms subsequent to the onset of amphetamine use were depression (79%), anxiety (76%), paranoia (52%), hallucinations (46%) and violent behavior (44%). All these symptoms increased in prevalence after the onset of amphetamine use. Addiction 1996 Jan;91(1):81-7, Psychological morbidity and route of administration among amphetamine users in Sydney, Australia. Hall W, Hando J, Darke S, Ross J.

Depression Much More Common in Cocaine Abusers: Opiate and sedative users had the least number of lifetime depressive episodes (3.7), and LSD and cocaine users had the greatest number (12.2). 375 drug abusers interviewed in treatment program. While author speculates drug use is a type of self-medication, this is highly speculative in this retro-spective study. Compr Psychiatry 1999 Jan-Feb;40(1):44-50; Brown U, Order of onset of substance abuse and depression in a sample of depressed outpatients. Abraham HD, Fava M.