A practical approach to prescribing antidepressants

PATIENTS WITH MAJOR DEPRESSION ONLY

For a patient presenting with depression but no other significant medical comorbidity, the first-line therapy is often an SSRI. Several generic SSRIs are available, and some are on the discount lists at retail pharmacies.

Symptoms should start to improve in about 2 weeks, and the optimal response should be achieved in 4 to 6 weeks of treatment. If this does not occur, consider either adding an augmenting agent or switching to a different antidepressant.

PATIENTS WITH CHRONIC PAIN

Chronic pain and depression often go hand in hand and can potentiate each other. When considering an antidepressant in a patient who has both conditions, the SNRIs and TCAs are typically preferred. Some SNRIs, namely duloxetine and milnacipran, are approved for certain chronic pain conditions, such as fibromyalgia. SNRIs are frequently used off-label for other chronic pain conditions such as headache and neuropathic pain.²

TCAs such as amitriptyline, nortriptyline, and doxepin are also often used in patients with chronic pain. These agents, like the SNRIs, inhibit the reuptake of serotonin and norepinephrine and are used off-label for neuropathic pain,^3,4 migraine, interstitial cystitis,⁵ and other pain conditions.^6–9

For TCAs and SNRIs, the effective dose range for chronic pain overlaps that for depression. However, TCAs are often given at lower doses to patients without depression. We recommend starting at a low dose and slowly titrating upward to an effective dose. SNRIs are often preferred over TCAs because they do not have anticholinergic side effects and because an overdose is much less likely to be lethal.

PATIENTS WITH SEXUAL DYSFUNCTION

One of the more commonly reported side effects of antidepressants is sexual dysfunction, generally in the form of delayed orgasm or decreased libido.¹⁰ Typically, these complaints are attributed to SSRIs and SNRIs; however, TCAs and MAO inhibitors have also been associated wth sexual dysfunction.

Both erectile dysfunction and priapism have been linked to certain antidepressants. In particular, trazodone is a known cause of priapism. Even if using low doses for sleep, male patients should be made aware of this adverse effect.

Switching from one agent to another in the same class is not likely to improve sexual side effects. In particular, all the SSRIs are similar in their likelihood of causing sexual dysfunction. In a patient taking an SSRI who experiences this side effect, switching to bupropion¹¹ or mirtazapine¹² can be quite useful. Bupropion acts primarily on dopamine and norepinephrine, whereas mirtazapine acts on serotonin and norepinephrine but in a different manner from SSRIs and SNRIs.

Adjunctive treatment such as a cholinergic agonist, yohimbine (contraindicated with MAO inhibitors), a serotonergic agent (eg, buspirone), or a drug that acts on nitric oxide (eg, sildenafil, tadalafil) may have some utility but is often ineffective. Dose reduction, if possible, can be of value.

PATIENTS WITH ANXIETY

Many antidepressants are also approved for anxiety disorders, and still more are used off-label for this purpose. Anxiety and depression often occur together, so being able to treat both conditions with one drug can be quite useful.¹³ In general, the antidepressant effects are seen at lower doses of SSRIs and SNRIs, whereas more of the anxiolytic effects are seen at higher doses, particularly for obsessive-compulsive disorder.¹⁴

First-line treatment would be an SSRI or SNRI. Most anxiety disorders respond to either class, but there are some more-specific recommendations. SSRIs are best studied in panic disorder, generalized anxiety disorder, social anxiety disorder, posttraumatic stress disorder, and obsessive-compulsive disorder. Fluoxetine, citalopram, escitalopram, and sertraline¹⁵ can all be effective in both major depressive disorder and generalized anxiety disorder. Panic disorder also tends to respond well to SSRIs. SNRIs have been evaluated primarily in generalized anxiety disorder but may also be useful in many of the other conditions.

Additionally, mirtazapine (used off-label)¹² and the TCAs^16–18 can help treat anxiety. Clomipramine is used to treat obsessive-compulsive disorder.¹⁹ These drugs are especially useful for nighttime anxiety, as they can aid sleep. Of note, the anxiolytic effect of mirtazapine may be greater at higher doses.

MAO inhibitors often go unused because of the dietary and medication restrictions involved. However, very refractory cases of certain anxiety disorders may respond preferentially to these agents.

Bupropion tends to be more activating than other antidepressants, so is often avoided in anxious patients. However, some research suggests this is not always necessary.²⁰ If the anxiety is secondary to depression, it will often improve significantly with this agent.

When starting or increasing the dose of an antidepressant, patients may experience increased anxiety or feel “jittery.” This feeling usually passes within the first week of treatment, and it is important to inform patients about this effect. “Start low and go slow” in patients with significant comorbid anxiety. Temporarily using a benzodiazepine such as clonazepam may make the transition more tolerable.

PATIENTS WITH CHRONIC FATIGUE SYNDROME OR FIBROMYALGIA

Increasing recognition of both chronic fatigue syndrome and fibromyalgia has led to more proactive treatment for these disorders. Depression can go hand in hand with these disorders, and certain antidepressants, namely the SNRIs, can be useful in this population.

More data exist for the treatment of fibromyalgia. Both duloxetine and milnacipran are approved by the US Food and Drug Administration (FDA) for the treatment of fibromyalgia.²¹ Venlafaxine is also used off-label for this purpose. SSRIs such as fluoxetine and citalopram have had mixed results.^21–23 TCAs have been used with some success; however, their side effects and lethal potential are often limiting.^21,24,25 A recent study in Spain also suggested there may be benefit from using MAO inhibitors for fibromyalgia, but data are quite limited.²⁶

The data for treating chronic fatigue syndrome with SSRIs, SNRIs, or MAO inhibitors are conflicting.^27–29 However, managing the co-existing depression may provide some relief in and of itself.