Reversible Inhibitors of Monoamine Oxidase Type A
Moclobemide
The most common side effects of moclobemide(Drug information on moclobemide) (not commercially available in the United States but available in Canada as Manerix) include dizziness, gastrointestinal upset, constipation, dry mouth, and headaches.[28] An initial dose of 100 mg/d and gradual titration to the maximum dose of 600 mg/d are recommended. Unlike the MAOIs, no dietary restrictions are necessary with moclobemide. Due to inhibited metabolism, the dosage of this drug should be reduced by 50% if the patient is also taking cimetidine. It should also not be combined with clomipramine(Drug information on clomipramine), dextromethorphan(Drug information on dextromethorphan), meperidine, and sympathomimetics such as over-the-counter cold preparations.
Tricyclic Antidepressants
As a class, TCAs have varying degrees of anticholinergic effects, increasing the risk of urinary retention, constipation, dry mouth, blurred vision, and cognitive impairment.[29] These agents may interact with antihypertensives, anticholinergics, anticoagulants, and anticonvulsants. Patients taking TCAs in addition to other anticholinergic medications are at risk for developing anticholinergic delirium. They are also associated with postural hypotension and dizziness, increasing the risks of falls and fractures, and should not be used in patients with narrow-angle glaucoma.
TCAs are highly cardiotoxic in overdose and known to occasion-
ally cause hyponatremia through SIADH[30]; they can also cause tachycardia. The quinidine(Drug information on quinidine)-like effects of these drugs can lead to arrhythmias. Therefore,
extreme caution is advised in patients with preexisting conduction defects,
precluding consideration if second- or third-degree heart block is present.
Desipramine
Of the tricyclic antidepressants, desipramine is thought to be the least likely to cause anticholinergic side effects. It can be started at 25 mg/d and increased to a maximum of 300 mg/d. (The geriatric dosage is usually 50 to 150 mg/d.)
Nortriptyline
This TCA causes sedation due to its H1-histamine-receptor blockade. For patients using a number of sedating medications (ie, narcotic analgesics, antiemetics, anxiolytics), the cumulative sedating effects of these drugs may become problematic. Nortriptyline(Drug information on nortriptyline) has least propensity for orthostatic, postural blood pressure changes. Dosing should start at 25 to 75 mg/d.[31]
Psychostimulants
For patients whose life expectancy is limited, psychostimulants (eg, dextroamphetamine, methylphenidate(Drug information on methylphenidate), pemoline(Drug information on pemoline)) offer an effective alternative due to their more rapid response rate.[32,33] In some patients, benefits may be seen within 48 hours. Psychostimulants have been shown to improve attention, concentration, and overall performance on neuropsychological testing in the medically ill.[34] They may even be beneficial in patients with mild cognitive impairment, and, when added to antipsychotics, can produce significant benefits in lethargic delirium. They can reduce the sedating effect of opioid analgesics, and may even provide some adjuvant analgesia themselves.[35] Stimulants can increase appetite, promote a sense of well-being, and improve feelings of weakness in cancer patients.
Side effects of psychostimulants include rare agitation, insomnia, or anxiety. If given within 6 to 8 hours of bedtime, insomnia can result, but this is easily avoided. They are generally well tolerated and rarely cause major problems. Mild increases in blood pressure, pulse rate, or tremor may be seen. Rarely, dyskinesias, paranoid psychosis, or exacerbation of an underlying confusional state may occur.
Dextroamphetamine or Methylphenidate
These medications can be initiated at a dose of 2.5 mg in the morning and at noon, and increased over several days to doses of 20 to 40 mg/d. If there is a good response, they may be continued for 1 or 2 months. Two-thirds of patients will be able to be withdrawn without a recurrence of depressive symptoms.[36] Should depression recur, one may continue their use for a year or more without significant abuse problems. In the event that tolerance develops, some dose adjustment may be required.
Pemoline
Compared to other psychostimulants, pemoline may be somewhat less potent and appears to have little abuse potential.[37] It also is not subject to the federal triplicate prescription regulation of other stimulants. The drug comes in a chewable tablet form that can be absorbed through the buccal mucosa, which is especially helpful if the patient has problems with swallowing. Dosing can begin at 18.75 mg in the morning and at noon, and increased gradually over several days, with most patients ultimately requiring 75 mg or less per day. Caution should be exercised in patients with liver impairment, and liver function tests monitored if treatment is to be continued over a prolonged period.[38]
Electroconvulsive Therapy
It is necessary to consider electroconvulsive therapy (ECT) in the following cases: (1) the treatment-resistant patient, (2) the patient who is psychotic or dangerously suicidal, and (3) the patient who is refusing to eat or drink. ECT has been shown to be a safe and effective treatment alternative, and may achieve more favorable responses than pharmacotherapy in medically compromised patients.[39]
Supportive Psychotherapy
Probably the most important aspect of psychotherapy is the therapeutic alliance (ie, the relationship between the patient and the caregiver). Fear of abandonment is common in severely ill patients; this fear is often based on the reality of seeing a social support network drop away over time. Psychotherapeutic relationships work best if they are based on mutual trust, respect, and sensitivity. Doctor and patient work together toward mutually agreed upon goals. Tailoring psychotherapy to the individual patient—considering personal style and unique needs—works best.
Supportive psychotherapy attempts to support adaptive coping mechanisms, minimize maladaptive ones, and decrease adverse psychological reactions such as fear, shame, self-loathing, and withdrawal.[40] The aim of such treatment is to bolster psychological equilibrium via the physician’s empathic posture in the context of a stable therapeutic relationship. Reassurance is useful when it is based on a specific understanding of the individual’s needs and is not clinically unrealistic. Psychoeducation is an important part of supportive psychotherapy. The caregiver should not adopt a stance that is overly solemn or emotionally restrained, because the patient may experience this as distancing. Moreover, patients should be encouraged to freely talk or ask questions about their prognosis (if they would like to), with the therapist taking an interested and interactive stance.[7]
Group Psychotherapy
Supportive group therapy is often helpful for patients to regain a sense of mastery and control by allowing patients to share common experiences, thereby reducing the sense of individual emotional isolation. Supportive/expressive group psychotherapy has been shown to improve mood, reduce maladaptive coping responses, and reduce pain in breast cancer patients.[41] Goals of supportive expressive groups include encouraging mutual support, detoxifying dying, enhancing communication with family and physicians, improving social networks, and examining life priorities.
