It is estimated that individuals making up approximately 17% of the population will experience clinical depression during their lifetime1 and that 1 in 8 people will be treated for a depressive episode at some point.2 Symptoms of depression can significantly impair patient functioning, personal and professional relationships, and overall quality of life. Furthermore, depression often is undertreated and misdiagnosed. Table 1 lists the diagnostic criteria for major depressive disorder, according to the Diagnostic and Statistical Manual of Mental Disorders, fourth edition.3
Depression is a chronic illness that is associated with significant morbidity and mortality. Compliance with medication is essential to prevent relapse and recurrence, especially because, as time progresses, episodes of depression may become longer in duration and may increase in severity.
Antidepressants are the mainstay of treatment, and their efficacy in reducing depressive symptoms has been demonstrated in both short- and long-term studies, with approximately 65% to 70% of patients experiencing significant reductions in symptoms. Response rates are similar for all of the currently available prescription antidepressants. Therefore, the decision as to which antidepressant should be used is based on other factors, including history of prior response, adverse effects, concurrent medications, and cost.4
Classes of Antidepressants
The monoamine hypothesis of depression states that depression is caused by a deficit in 1 or more of the following neurotransmitters: serotonin (5-HT), norepinephrine (NE), and/or dopamine (DA). All currently marketed antidepressants work by increasing 1 or more of these neurotransmitters. Antidepressants fall into a variety of pharmacologic classes: (1) monoamine oxidase inhibitors (MAOIs); (2) tricyclic antidepressants (TCAs); (3) selective serotonin reuptake inhibitors (SSRIs); (4) serotonin and norepinephrine reuptake inhibitors (SNRIs); (5) serotonin-2 antagonist/reuptake inhibitors (SARIs); (6) norepinephrine and dopamine reuptake inhibitors (NDRIs); and (7) noradrenergic and specific serotonergic antidepressants (NaSSAs).5
The classic antidepressants include the MAOIs and the TCAs, but they have largely been replaced by the newer antidepressants because of better side-effect profiles. The MAOIs work by blocking the metabolism of 5-HT, NE, and DA, but, due to dietary restrictions and drug interactions, these medications are rarely used in clinical practice.
The main therapeutic actions of the TCAs appear to be 5-HT and NE reuptake inhibition. The TCAs cause many adverse effects, however, including weight gain, constipation, blurred vision, dry mouth, and orthostatic hypotension. Higher doses can lead to lethal cardiac arrhythmias and seizures. These medications are no longer first-line treatments for depression.
The SSRIs work by selectively inhibiting the reuptake of 5-HT, and they are devoid of many of the adverse effects of the older antidepressants. In particular, they are not lethal in overdose, and they lack significant cardiac toxicity. Adverse effects that are associated with the SSRIs include anxiety, insomnia, sexual dysfunction, and gastrointestinal (GI) disturbances (eg, nausea and diarrhea). Taking SSRIs with food or a snack may help limit GI irritation.
The pharmacology of venlafaxine (an SNRI) is dosedependent (ie, at low doses it increases 5-HT, and at medium-to-high doses it increases NE). The side effects of venlafaxine are similar to those of the SSRIs, but it also may cause constipation and dry mouth.
Nefazodone (an SARI) acts as a 5-HT reuptake inhibitor and a 5-HT2 receptor antagonist. Blockade of the 5-HT2 receptor may help reduce anxiety and insomnia associated with 5-HT2 stimulation. The pharmacist should be sure to caution patients about the symptoms of liver failure (eg, jaundice, malaise, anorexia) that may appear while they are taking nefazodone, since cases have been reported.
Bupropion (an NDRI) is a unique antidepressant in that it does not have significant effects on 5-HT transmission (ie, it exerts its effects by increasing NE and DA). Side effects include stimulation, insomnia, and nausea. Mirtazapine (an NaSSA) disinhibits neurotransmission and is both pronoradrenergic and proserotonergic due to its blockade of alpha2 receptors.
Mirtazapine also blocks histamine receptors, leading to weight gain and sedation, and it blocks 5-HT3 receptors, potentially leading to decreased GI side effects. Table 2 lists some of the most commonly used antidepressants.
The Role of the Pharmacist
Regardless of which antidepressant is being used, the pharmacist should explain to the patient that it usually takes at least 2 weeks for medications to exert antidepressant activity (ie, reduction in depressive symptoms), and it may take longer for a full response (ie, remission). It also is important to explain to the patient that many of the side effects that occur initially in treatment often subside. The pharmacist should discuss the goals of treatment with the patient-which should ultimately be the full remission of symptoms and a complete return of psychosocial functioning.2 Finally, the pharmacist should counsel patients that, even after their mood has improved, it is crucial that they continue their antidepressant for at least 6 to 9 months to prevent recurrence of the depression. Some patients may require indefinite treatment.4
A supportive relationship between the clinician and the patient can help improve treatment compliance.6 Pharmacists are in an ideal situation to improve compliance by educating patients and clinicians regarding the characteristics of depression and by establishing a supportive relationship with patients being treated with antidepressant medications.