Treatment Implications in Depression Subtyping

Abstract & Commentary

Synopsis: Assessment of the subtype of depression may be useful in guiding treatment, if time allows.

Source: Clayton PJ. Depression subtyping: Treatment implications. J Clin Psychiatry 1998;59(suppl 16):5-12.

Management of depression in the primary care setting can be enhanced by determining the subtype of a patient’s depression and by applying the treatment with the highest likelihood of success. Most primary care physicians use selective serotonin reuptake inhibitors (SSRIs) because of convenient dosing and a reasonable side effect profile, or the tricyclic antidepressants (TCAs) because of familiarity. Indeed, these medications are effective for a wide range of conditions but many times may not be optimal. This paper describes the range of unipolar depressive disorders, including subtypes of anxious depression, atypical depression, seasonal affective disorder (SAD), and postpartum depression. Diagnostic features that distinguish the subtypes and the literature regarding the efficacy of treatments are reviewed. Anxious depression consists of anxiety symptoms accompanying depression in the form of panic attacks, worries, tension or restlessness, phobias, or compulsions. These patients have a slower response to treatment, a poorer overall response to treatment, and a higher rate of suicide in the first year of their illness. Most, if not all, antidepressants have been shown to be effective for anxious depression, including TCAs, monoamine oxidase inhibitors (MAOIs), SSRIs, and newer antidepressants such as nefazodone (Serzone), venlafaxine (Effexor), and mirtazepine (Remeron). Atypical depression is characterized by mood reactivity and at least two of the following features: increased appetite, weight gain, hypersomnia, leaden paralysis, and sensitivity regarding interpersonal rejection. It is more common in females and has an unusually chronic course. In comparison to melancholic depression, patients with atypical depression have an earlier onset, more frequent dysphoric mood, more chronic course, more family members with dysthymia, and preferential response to MAOIs. SSRIs have also been shown to be effective in atypical depression. SAD is considered when all or the majority of a patient’s depressive episodes occur from November through April. Most patients have increased appetite, carbohydrate craving, weight gain, and hypersomnia. This composite of symptoms is sometimes called "reverse vegetative symptoms," since it is the opposite of "typical" depression. Effective treatments used singly or in combination include light therapy, sleep deprivation, SSRIs, and MAOIs. Postpartum depression is a depressive episode within four weeks postpartum. Its incidence is unknown, though a study of more than 1500 Swedish women revealed a point prevalence of 12.5% at eight weeks and 8.3% at 12 weeks. Symptoms of depressed mood, tearfulness, and labile mood tend to peak five days postpartum and persist thereafter. Postpartum depression can be treated with psychotherapy, medication, or light therapy (if seasonally related). Few data are available assessing the efficacy of medication treatments. With regard to safety when breastfeeding, TCAs (amitriptyline, nortriptyline, desipramine, clomipramine) and sertraline are not found in infant plasma, but other drugs have been detected in breast milk and infant plasma. Clayton concludes that determining the subtype of depression is an important step in making an accurate diagnosis, which facilitates the most appropriate treatment(s). However, the best treatment for individual patients should be made on a case-by-case basis.

Comment by Donald m. Hilty, MD

It is easy to recommend, but perhaps not reasonable to expect, that primary care physicians subtype their patients with depression because of the tremendous number of competing demands for time in the primary care setting. To the degree that it can be done, patients will no doubt benefit. An alternative approach is to have primary care physicians consistently use a single treatment (e.g., SSRIs) that is familiar to them and apply a few rules of thumb to address special considerations or exceptions regarding that treatment. The first rule of thumb for primary care physicians is to use SSRIs as the first-line antidepressant treatment since they appear efficacious for all subtypes. They also have a reasonable side effect profile, few medical contraindications, an easy dosing regimen, and low potential for overdose. SSRIs are not the first-line treatment in the following situations: mothers breast-feeding infants (except with sertraline); a personal and family history of response that suggests another medication has worked well; significant drug interactions; cost; or a concern of the patient regarding a particular side effect (e.g., sexual dysfunction). The second rule of thumb is that patients with anxious depression require increased vigilance on behalf of the primary care physicians. They may require a longer trial of antidepressants. It appears that SSRIs, nefazodone, and mirtazepine reduce anxiety as early as seven days after initiation, but these patients may also benefit from a short-term (2-4 weeks) trial of benzodiazepines. The third rule of thumb is that the antidepressant needs to be user friendly. TCAs are often not prescribed in therapeutic doses by primary care providers because of side effects and the necessity to titrate the dose. MAOIs are not particularly feasible because of dietary restrictions. The fourth rule of thumb is that the newer antidepressants (nefazodone, venlafaxine, and mirtazepine) are not identical to SSRIs in terms of mechanisms of action or side effects. Their serotonergic effects account for the preliminary data suggesting efficacy for anxious depression and, perhaps, the other subtypes already mentioned. The efficacy of bupropion (Wellbutrin), which modulates norepinephrine and dopaminergic transmission, is not known for these subtypes. More systematic data are needed regarding the efficacy of these medications for atypical, seasonal, and postpartum subtypes of depression.