A practical approach to prescribing antidepressants
ABSTRACTAlthough antidepressant drugs do not differ much in their efficacy rates, the particular characteristics of one drug may make it a better choice in a given patient. This article provides insight into the art of prescribing antidepressants in primary care, with recommendations for prescribing for patients with chronic pain, sexual dysfunction, anxiety, chronic fatigue syndrome, fibromyalgia, severe insomnia, old age, diabetes, and heart problems.
KEY POINTS
- We suggest that clinicians become familiar with one drug from each class of antidepressants.
- Many antidepressants are also approved for conditions other than depression, and for patients who have both depression and one or more of these comcomitant conditions, these drugs can have a “two-for-one” benefit.
- Adverse effects of an antidepressant are usually predictable on the basis of the drug’s mechanism of action.
PATIENTS WITH FREQUENT INSOMNIA
Insomnia can be a symptom of depression, but it can also be a side effect of certain antidepressants. The SSRIs and SNRIs can disrupt sleep patterns in some patients by shortening the rapid-eye-movement (REM) stage.30,31
In patients with severe insomnia, it may be best to first recommend taking the antidepressant in the morning if they notice worsening sleep after initiating treatment. Patients can be told with any antidepressant, “If it makes you tired, take it at night, and if it wakes you up, take it in the morning.” Of note, a recent South African study suggested that escitalopram may be able to improve sleep.32
If that does not solve the problem, there are other options. For instance, mirtazapine, particularly in doses of 15 mg or 30 mg, aids depression and insomnia. At higher doses (45 mg), the sleep-aiding effect may be reduced. Low doses of TCAs, particularly doxepin, maprotiline (technically speaking, a tetracyclic antidepressant), amitriptyline, and nortriptyline can be effective sleep aids. These agents may be used as an adjunct to another antidepressant to enhance sleep and mood. However, the TCAs also shorten the REM stage of sleep.33
The previously mentioned drug interactions with SSRIs and SNRIs also need to be considered. Caution should be used when discontinuing these medications, as patients may experience rebound symptoms in the form of much more vivid dreams. MAO inhibitors may worsen insomnia because they suppress REM sleep.34
Trazodone is another agent that at lower doses (25–150 mg) can be an effective, nonaddicting sleep aid. When used as an antidepressant, it is generally prescribed at higher doses (300–400 mg), but its sedating effects can be quite limiting at these levels. It is important to remember the possibility of priapism in male patients.
GERIATRIC PATIENTS
Old age brings its own set of concerns when treating depression. Elderly patients are more susceptible to potential bradycardia caused by SSRIs. The TCAs have the more worrisome cardiac side effect of QTc prolongation. TCAs can slow cognitive function, whereas the SSRIs, bupropion, and the SNRIs tend not to affect cognition. Escitalopram and duloxetine have been suggested to be particularly effective in the elderly.35,36 A study from the Netherlands linked SSRIs with increased risk of falling in geriatric patients with dementia.37 Constipation, which could lead to ileus, is increased with TCAs and certain other agents (ie, paroxetine) in the geriatric population.
Mirtazapine is often very useful in elderly patients for many reasons: it treats both anxiety and depression, stimulates appetite and weight gain, can help with nausea, and is an effective sleep aid. Concerns about weight, appetite, and sleep are particularly common in the elderly, whereas younger patients can be less tolerant of drugs that make them gain weight and sleep more. Normal age-related changes to the sleep cycle contribute to decreased satisfaction with sleep as we age. In addition, depression often further impairs sleep. So, in the elderly, optimizing sleep is key. Research has also shown mirtazapine to be effective in patients with both Alzheimer dementia and depression.38
DIABETIC PATIENTS
One of the more worrisome side effects of psychiatric medications in diabetic patients is weight gain. Certain antidepressants have a greater propensity for weight gain and should likely be avoided as first-line treatments in this population.12 Typically, these agents include those that have more antihistamine action such as paroxetine and the TCAs. These agents also may lead to constipation, which could potentially worsen gastroparesis. Mirtazapine and the MAO inhibitors are also known to cause weight gain.
Bupropion and nefazodone are the most weight-neutral of all antidepressants. Nefazodone has fallen out of favor because of its potential to cause fulminant liver failure in rare cases. However, it remains a reasonable option for patients with comorbid anxiety and depression who have significant weight gain with other agents.
SSRIs and MAO inhibitors may improve or be neutral toward glucose metabolism, and some data suggest that SNRIs may impair this process.39
PATIENTS WITH CARDIAC CONDITIONS
Major depression often coexists with cardiac conditions. In particular, many patients develop depression after suffering a myocardial infarction, and increasingly they are being treated for it.40 Treatment in this situation is appropriate, since depression, if untreated, can increase the risk of recurrence of myocardial infarction.41
However, there are many concerns that accompany treating depression in cardiac patients. Therefore, a baseline electrocardiogram should be obtained before starting an antidepressant.
TCAs and tetracyclic agents have a tendency to prolong the QTc interval and potentiate ventricular arrhythmias,42 so it may be prudent to avoid these in patients at risk. These agents can also significantly increase the pulse rate. This tachycardia increases the risk of angina or myocardial infarction from the anticholinergic effects of these drugs.
In February 2013, the FDA issued a warning about possible arrhythmias with citalopram at doses greater than 40 mg in adult patients43; however, research has suggested citalopram is effective in treating depression in cardiac patients.44 Research has not shown an increase in efficacy at doses greater than 40 mg daily, so we recommend following the black-box warning.
TCAs and MAO inhibitors can also cause orthostatic hypotension. On the other hand, consuming large amounts of tyramine, in foods such as aged cheese, can precipitate a hypertensive crisis in patients taking MAO inhibitors.
Which antidepressants tend to be safer in cardiac patients? Sertraline has been shown to be safe in congestive heart failure and coronary artery disease,45–47 but the SSRIs are typically safe. Fluoxetine has shown efficacy in patients who have had a myocardial infarction.48 Mirtazapine has also been shown to be efficacious in cardiac patients.49 Nefazodone, mirtazapine, bupropion, SSRIs, and SNRIs have little or no tendency toward orthostatic hypotension.
