Stimulants’ immediate onset of action may be particularly useful in terminally ill patients who suffer from fatigue or depression. A double-blind, placebo-controlled, randomized study demonstrated that augmenting citalopram, 20 to 40 mg/d, with methylphenidate, mean dose 15 mg/d, for 3 weeks in older depressed patients significantly improved treatment response and accelerated time to remission compared with citalopram and placebo.16 However, a recent Cochrane review did not show clear efficacy for psychostimulants to treat depression.17
Fatigue. Along with depression, fatigue frequently is seen in older patients with medical illnesses. Mood disorders, medical comorbidities, and sleep disturbances are linked to fatigue. Underlying medical causes such as hypothyroidism, anemia, and electrolyte imbalances should be ruled out before starting a psychostimulant. A review by Minton et al18 that looked at cancer-related fatigue suggested that methylphenidate can be beneficial, although the evidence is mixed.
Interferon-alpha treatment for hepatitis C can cause depression and fatigue, and psychostimulants may help treat fatigue-related side effects.19 Fatigue may present as an isolated symptom in interferon-alpha treatment and psychostimulant use may prevent patients from taking an additional medication, therefore decreasing the risk of further side effects.
Fall risk. Some evidence supports using psychostimulants to lower the risk of falling and hypoactive delirium. A recent review by Elie et al20 concluded that stimulants could improve cognitive function in end-of-life hypoactive delirium. Additionally, a randomized, placebo-controlled, double-blind study that evaluated fall risk concluded that methylphenidate, 20 mg/d, might improve some aspects of executive function and gait stability in older adults.21 The authors hypothesized that improved cognition associated with psychostimulant use may play a role in improving fall risk.
Safety concerns
Clinicians should be aware of safety considerations and possible side effects when prescribing psychostimulants. Psychostimulants are controlled substances and are subject to restrictions (Box 3).22 In 2007, the FDA issued warnings regarding an association between psychostimulant use and sudden death, myocardial infarction, and stroke in patients with preexisting cardiac abnormalities or heart problems.23 Also, some evidence indicates that psychostimulants can increase heart rate and systolic blood pressure. These parameters should be monitored during treatment. Reducing or stopping psychostimulants generally reverses cardiovascular effects. Although the evidence to support these events appears sparse, perform a thorough history before beginning a stimulant and make appropriate referrals as indicated. In November 2011, the FDA reported that psychostimulant use in children and young adults is not associated with adverse cardiovascular events, including stroke, heart attack, and sudden cardiac death.24
Less common side effects reported with psychostimulants include anxiety, insomnia, hallucinations, anorexia, delirium, palpitations, and headache. A meta-analysis of studies of adults with ADHD found that adverse events related to psychostimulants were relatively rare; the most common side effects were diminished appetite and difficulty sleeping.25 Sleep-related side effects can be avoided by dosing these medications earlier in the day, typically before 5 pm. Herrmann et al5 reported 2 cases of apparent delirium and 1 with irregular heartbeat in patients with DAT taking methylphenidate vs placebo. However, most patients in this study experienced mild or no adverse events.
Other safety concerns involve using methylphenidate in patients with glaucoma. In theory, stimulants could exacerbate an acute attack of glaucoma in patients with narrow-angle glaucoma. Patients at risk should be referred to an ophthalmologist for an assessment.
Review other medications the patient is taking and assess for possible drug-drug interactions. Combining monoamine oxidase inhibitors (MAOIs) and methylphenidate warrants caution because of the risk of serotonin syndrome and hypertensive crisis. However, there are case reports of successful MAOI/methylphenidate therapy.26 Additionally, methylphenidate increases levels of warfarin and tricyclic antidepressants when taken with these agents.27 Psychostimulants generally are well tolerated by most individuals and taking a careful history may help prevent adverse events.
Psychostimulants: Prescribing limitations
As schedule II controlled substances, psychostimulants are subject to prescribing limitations. The current Drug Enforcement Administration (DEA) policy on schedule II controlled substances allows for the equivalent of a 90-day supply of medication to be written with multiple prescriptions. DEA requirements for multiple prescriptions include:
- Each prescription issued is for a legitimate medical purpose by an individual practitioner acting in the usual course of his/her professional practice
- The individual practitioner must provide written instructions on each prescription indicating the earliest date on which a pharmacy may fill each prescription
- The issuance of multiple prescriptions is permissible under applicable state laws
- The individual practitioner fully complies with all other applicable requirements under the Controlled Substances Act and implementing regulations, as well as any additional requirements under state law.22