New research from the University of California, San Diego has indicated that methylphenidate may be an effective and rapid-acting option for the treatment of depression in hospice patients. Dr. Scott Irwin, director of phychiatry programs at the Institute for Palliative Medicine at San Diego Hospice and faculty psychiatrist at UCSD, presented the results of his research at the 2012 Annual Assembly of the American Academy of Hospice and Palliative Medicine.
Depression is notoriously difficult to treat in the hospice setting because the available treatment modalities take so long to work. Most antidepressants can be expected to reach their peak effects in 6-8 weeks, and during this waiting period, side effects of the antidepressant medications are at their peak and are often intolerable. In the United States, the median hospice stay is only about 3 weeks, so available antidepressants simply don’t cut it. With the prevalence of depression in palliative care estimated at 15%, we are in dire need of medications that have results in days, not weeks.
Methylphenidate, a psychostimulant most commonly used in the treatment of ADD and ADHD, has been under investigation for quite some time as either monotherapy for depression or as an adjunct to other antidepressants, such as SSRIs, in order to accelerate the onset of action. Interest in methylphenidate is driven by the potential to rapidly produce clinical effects and to alleviate other concomitant symptoms such as fatigue, sedation and poor concentration. The research that has been conducted has been in small-scale studies or retrospective trial designs. This research, though not very robust, does seem to indicate a role for methylphenidate in the treatment of depression, and this role continues to be defined with studies such as that conducted by Dr. Irwin.
Dr. Irwin’s study included 64 palliative care patients with depression who underwent treatment with either methylphenidate, an SSRI, another antidepressant, or usual care alone (no medication). Almost all of the patients (20 out of 21, or 95%) in the methylphenidate group had a significant clinical response as measured by the Clinical Global Impressions Scale (CGI), with an average onset of action of 4 days. By comparison, 4 of 9 SSRI-treated patients (44%) responded, onset 10 days; 3 of 13 patients (23%) treated with other antidepressants responded, onset 4 days (these are more rapid onsets than would be expected for standard antidepressants, for unknown reasons); and 0 of 21 usual care patients responded. Side effects were more common with methylphenidate – 1.72 versus 1.13 on the CGI – however, these side effects were mild.
Previous trials have found similar results indicating the efficacy of methylphenidate in the treatment of depression. In a 2001 trial of 36 cancer patients treated with methylphenidate, 30 patients completed the trial with 21 responding within 3 days and the other 9 responding by day 5. As expected, fatigue, concentration, and sedation also improved in some of the patients. The six patients who did not complete the trial withdrew due to side effects.
Because this is off-label use, there are no published dosing guidelines. But based on the available references, the effective methylphenidate dose for depression seems to be in the range of 10-40 mg daily. A good starting dose of methylphenidate would be 5 mg BID (first dose upon awakening, second dose around noon), followed by rapid titration to effect. One of the benefits of methylphenidate is that you know within days, not weeks, whether it is working. In the 2001 trial summarized above, methylphenidate was started at a dose of 5 mg BID and titrated up to 10 mg BID if the patient had not responded by day 3. Dr. Irwin reported he is now conducting a prospective study using flexible dosing with dosing changes on days 3, 7 and 14 and a maximum dose of 20 mg BID.
Close monitoring of side effects is recommended. Cardiovascular stimulation including elevated blood pressure and tachycardia are common, so methylphenidate should probably be avoided in patients with severe cardiovascular disease. CNS stimulation is also common, so watch for anxiety and insomnia. It is unclear from the available research what effect methylphenidate will have on appetite in hospice patients. In the general population, methylphenidate tends to decrease appetite, but some of the small-scale trials of methylphenidate in patients with cancer have found improved appetite, which may be due to improvement in depression.
Emptage RE, Semla TP. Depression in the medically ill elderly: a focus on methylphenidate. Annals of Pharmacotherapy 1996; 30: 151-157.
Homsi J, Nelson KA, Sarhill N, et al. A phase II study of methylphenidate for depression in advanced cancer. American Journal of Hospice and Palliative Care 2001; 18: 403-407.
Homsi J, Walsh D, Nelson KA, LeGrand S, Davis M. Methylphenidate for depression in hospice practice: A case series. American Journal of Hospice and Palliative Care 2000; 17: 393-398.
Katon W, Raskind M. Treatment of depression in the medically ill elderly with methylphenidate. The American Journal of Psychiatry 1980; 137: 963-965.
Macleod AD. Methylphenidate in terminal depression. Journal of Pain and Symptom Management 1998; 16: 193-198.
Rozans M, Dreisbach A, Lertora JJL, Kahn MJ. Palliative uses of methylphenidate in patients with cancer: A review. Journal of Clinical Oncology 2002; 20: 335-339.
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Posted on May 2, 2012
|The effect of methylphenidate on fatigue and depression in hospice patients has also been demonstrated in a small randomized, double-blinded, placebo controlled study published in the Journal of Pain and Symptom Management by Kerr et al. early this year. Doses were titrated up every 3 days as tolerated to a maximum of 40mg/day. Although the trial was small, a dose relationship was found between symptom improvement and drug dose.
-- Natalie Latuga, PharmD
Posted 5/3/2012 10:32:00 AM
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