Using Psychostimulants to Treat Depression in the Medically Ill

Lessons Learned at the Interface of Medicine and Psychiatry

The Psychiatric Consultation Service at Massachusetts General Hospital (MGH) sees medical and surgical inpatients with comorbid psychiatric symptoms and conditions. Such consultations require the integration of medical and psychiatric knowledge. During their thrice-weekly rounds, Dr. Huffman and Dr. Stern discuss the diagnosis and management of conditions confronted. These discussions have given rise to rounds reports that will prove useful for clinicians practicing at the interface of medicine and psychiatry.

Have you ever wondered if there is a class of antidepressants that works within days instead of weeks or months? Have you considered using psychostimulants in the medically ill but weren't sure if it would be safe? These issues are framed by the following case presentation of an elderly man with symptoms of major depressive disorder that complicated his recovery from respiratory failure. A discussion of the use of psychostimulants in medically ill patients follows the case presentation; a brief annotated bibliography is also included.

Case Presentation

Mr. A, a 71-year-old man with a history of chronic obstructive pulmonary disease (COPD), hypertension, and hypercholesterolemia was admitted to the hospital for the treatment of a COPD exacerbation. When his symptoms of COPD worsened on the third day of hospitalization, he was transferred to the intensive care unit and intubated. He remained intubated for 6 days, and his respiratory function improved enough to allow for extubation. Mr. A slowly recovered, but by the fifth day of hospitalization, he appeared withdrawn, apathetic, and dysphoric. His appetite had waned, as had his participation in his daily regimen of chest physical therapy. Psychiatric consultation was requested for evaluation of depression. Finding symptoms of major depressive disorder, poor oral intake, and limited participation in his medical and rehabilitative care, the consultant psychiatrist considered prescribing a psychostimulant.

Why Are Psychostimulants Used in the Treatment of Depression?

Psychostimulants effectively treat acute depression. These agents are rapidly acting (frequently having a therapeutic effect within 48 hours) and have been well tolerated in a variety of settings and patient populations. Stimulants should be considered in the treatment of any patient with depression. This class of medications may be particularly useful, however, in situations in which rapid recovery is essential. Psychostimulant treatment may be especially warranted when depression has led to poor nutritional intake in medically fragile patients, limited participation in crucial rehabilitation activities (e.g., poststroke physical therapy and occupational therapy), and impaired decision-making capacity during times when key medical decisions need to be made.

What Populations Have Benefited From the Use of Psychostimulants?

A wide variety of patient populations have benefited from the use of psychostimulants. Dextroamphetamine and methylphenidate, the 2 most frequently used stimulants, have been studied in a number of prospective and retrospective trials. Among medically healthy patients, stimulants have been used to treat children and adolescents with attention-deficit/hyperactivity disorder, to augment the treatment of major depressive disorder in adults, and to treat depression in the elderly.

Stimulants have also been used safely and effectively for those with poststroke depression, for those with human immunodeficiency virus (HIV)-associated depression, and for those who have difficulty weaning from mechanical ventilation. Furthermore, numerous studies of patients with cancer and depression have found that stimulants improve mood and other symptoms associated with major depressive disorder; a retrospective chart review by Olin and Masand¹ found that more than 80% of cancer patients responded favorably to use of methylphenidate. Stimulants have also effectively treated cognitive disturbances in patients with HIV infection and in cancer patients undergoing cranial radiation.

Among acutely depressed medical inpatients, psychostimulants are also safe and effective. Woods and coworkers² completed a retrospective study of 66 medical and surgical inpatients at Massachusetts General Hospital (MGH) treated with psychostimulants (mean age of 72 years). The authors found that 48% of the stimulant trials resulted in marked or moderate improvement and that 73% of the trials resulted in at least some improvement of depressive symptoms. Only 7% of the trials were discontinued because of side effects, none of which were life-threatening. Notably, the effects of stimulants upon heart rate and blood pressure were minimal, and appetite in these patients actually increased (in conjunction with the treatment of their depression).

Despite these favorable data on the use of psychostimulants in the treatment of depression, larger double-blind, placebo-controlled trials are still needed to confirm their efficacy, to delineate their side effect profiles, and to determine their optimal dosing regimens.

What Are Contraindications to the Use of Psychostimulants?

There are few absolute contraindications to the use of psychostimulants in the treatment of depression. Several conditions should be considered, however, as relative contraindications. Some relatively contraindicated conditions center around the potential of psychostimulants to raise blood pressure and heart rate. Although elevation of blood pressure and heart rate has, in general, been minimal at MGH, the presence of several conditions (e.g., recent myocardial infarction, ongoing congestive heart failure, low ejection fraction, uncontrolled hypertension or tachycardia, or a history of ventricular arrhythmia) may place an individual at risk for adverse events when even small changes in these parameters develop. In addition, it is prudent to avoid the use of stimulants in hyperdynamic states, such as hyperthyroidism. In these cases, one may consider the administration of a stimulant to be a small “cardiac stress test.” When using stimulants in patients with any of these conditions, one should dose stimulants more cautiously and check vital signs more frequently.

Furthermore, the administration of stimulants should be avoided in patients who have been treated with monoamine oxidase inhibitors within the previous 2 weeks, who are pregnant (since there are no data in humans regarding the safety of stimulants in pregnancy), who have a history of adverse reaction to stimulants, or who have a history of stimulant abuse.

How Are Stimulants Dosed, and How Are Side Effects Monitored in Depressed Populations?

Dosing of psychostimulants can begin with a single 5-mg dose of dextroamphetamine or methylphenidate, given orally in the morning. If the patient is medically fragile or is at some elevated risk of having an adverse reaction, one can begin with a 2.5-mg dose. The peak effect of these medications occurs in 2 to 4 hours. Therefore, mood and vital signs should be evaluated 2 to 4 hours after the dose to assess the effect of the stimulant on these parameters. If there is no response, the next morning's dose can be doubled. The dose may be increased by 5 mg/day until a response is achieved, intolerable side effects occur, or a dose of 20 mg is reached. Most practitioners would consider no response after a dose of 20 mg to be a failed trial.

If depressive symptoms improve, and this improvement lasts throughout the day, once-daily administration should be continued. If there is initial improvement of mood and energy that wanes in the afternoon, the same dose used in the morning can be repeated in the early afternoon. Late afternoon or evening administration should be avoided because use of stimulants may interfere with sleep.

The appropriate duration of psychostimulant therapy remains open to debate. In the MGH study,² most patients received stimulants only until their hospital discharge. A small subset of those studied remained on the medication for 2 to 3 weeks after discharge, while a few remained on the medication for more than a year.

Should Psychostimulants Be Used for Mr. A?

Mr. A would be considered a good candidate for psychostimulant treatment of his depressive symptoms on the basis of the information presented here. He had no obvious contraindication to the use of stimulants, and he would most likely have benefited from their rapid onset of action. This rapid effect would have been particularly important for him because his poor appetite and inability to participate in his care were contributing to a suboptimal medical outcome. He could have been started at either 2.5 or 5 mg of dextroamphetamine or methylphenidate. His vital signs should have been monitored closely (especially during the first few hours following a dose), given his medical fragility. Both the literature on psychostimulants and our experience suggest that he would have tolerated this treatment well and had an excellent chance of responding rapidly to treatment.

Drug names: dextroamphetamine (Dexedrine and others), methylphenidate (Ritalin, Concerta, and others), pemoline (Cylert).