Though major depressive disorder (MDD) is one of the most common mental disorders in the United States, significant reduction in symptoms is possible for 70–80% of affected individuals if they receive appropriate treatment. Therefore, it is of prime importance for healthcare providers to stay informed about the condition and to keep abreast of developments in treatments for MDD.

Stay current on Psychiatry topics; attend a specialty-specific conference.

Clinical depression is more extreme than everyday sadness. A major depressive episode is defined as a period of two weeks or longer during which a patient experiences a depressed mood or loss of interest or pleasure, and has at least four other symptoms reflecting a functional change, such as problems with sleep, eating, or concentration. An individual experiencing depression may develop serious, long-lasting symptoms that impede their ability to participate in regular life activities. The number of those who endure this type of impairment is significant, with approximately one in five individuals having depressive disorders, including MDD, dysthymia, or subsyndromal depression.

Results from the Substance Abuse and Mental Health Services Administration’s 2012 National Survey on Drug Use and Health conveyed the widespread impact of depression in the United States, estimating that:

• 2.2 million adolescents aged 12 to 17 had at least one major depressive episode in the prior year, representing 9.1% of that age group
• 1.5 million adolescents aged 12 to 17 had at least one major depressive episode with severe impairment in the prior year, representing 6.3% of that age group
• 16 million adults aged 18 or older had at least one major depressive episode in the prior year, representing 6.9% of all adults

The CDC’s National Center for Health Statistics reported that:

• From 2007–2010, the prevalence of depression in any two-week period, among persons aged 12 years and older, was 8%
• In 2010, major depressive disorder was the first-listed diagnosis for 395,000 hospital patients
• In 2011, suicide deaths totaled 39,518, or 12.7 per 100,000 individuals

Antidepressants succeed in reaching a high response rate; most first- and second-generation antidepressants achieve an approximate 60% response rate in adults with MDD. Since first-generation antidepressants often have intolerable side effects and a high risk for harm when taken in excess or in combination with certain medications, second-generation antidepressants are favored. PDR’s Antidepressants table, which is based on FDA-approved labeling as of March 2014 and is included as part of the 2015 PDR Nurse’s Drug Handbook, contains select information on available antidepressants. In general, first-generation antidepressants, which are older and less commonly used, include tricyclics and monoamine oxidase inhibitors. The more commonly used medications are all second-generation, and are classified as selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), atypical antidepressants, or serotonin modulators. Medications within a particular class are chemically related and function in a similar way, therefore healthcare providers can select to prescribe them based on:

• The previous response of the patient to antidepressants
• Side effects of the drug and possible interactions with other medications the patient is taking
• Patient’s symptoms and other conditions
• Patient’s preference, level of difficulty to take the drug, and cost of the drug

It is important to keep in mind that the individual response to pharmacotherapy can be different in each patient. Full response time can take up to 12 weeks, though many do have improvement within one to two weeks. Dose modification may need to be considered if a patient does not experience any or much symptom relief after four to six weeks. As initial treatment of severe depression, SNRIs or SSRIs are recommended. If symptoms besides those for depression exist, additional therapy may be appropriate. Special care should be taken when prescribing tricyclics, as they can cause serious side effects.

Some of the more recently approved products include the following:

• First generic versions of Cymbalta (duloxetine) – Aurobindo Pharma Ltd., Dr. Reddy’s Laboratories Ltd., Lupin Ltd., Sun Pharma Global FZE, Teva Pharmaceuticals USA, and Torrent Pharmaceuticals Ltd. received FDA approval to market the SNRI duloxetine in various strengths
• Fetzima (levomilnacipran) – once-daily SNRI, unique from others because it inhibits reuptake of norepinephrine to a greater extent than serotonin
• Brintellix (vortioxetine) – atypical antidepressant that functions as a serotonin modulator and stimulator with a majority of activity geared toward serotonin and 5-HT receptors; also thought to affect adrenergic receptors to less of a degree as well as concentrations of acetylcholine and histamine
• Viibryd (vilazodone hydrochloride) – SSRI/5-HT_1A-receptor partial agonist; not associated with significant weight gain or sexual dysfunction

Other drugs approved in or before 2013:

• Cymbalta (duloxetine) – SNRI used to treat major depression, neuropathic pain, generalized anxiety, fibromyalgia, and other conditions; unique due to its pain relief characteristics
• Emsam (selegiline) – MAOI available as a transdermal patch, which allows for bypassing the small intestine, bypassing the liver, and preventing a hypertensive crisis (associated with MAOIs)
• Oleptro (trazodone) – triazolopyridine derivative, available as an extended-release pill
• Pristiq (desvenlafaxine) – SNRI that is an improved version of Effexor and contains the synthetic active metabolite that results in an antidepressant effect
• Khedezla (desvenlafaxine) – SNRI used for the treatment of MDD

Keep informed by using PDR.net as a resource for antidepressants, as well as thousands of other available products. Stay current on alerts and specific product labeling by providing updated contact information. To have updated drug information, full labeling, and safety warnings integrated into your electronic prescribing system automatically, and at no cost to you, be sure to request PDR drug data feeds, including PDR BRIEF.

Salvatore Volpe, MD, FAAP, FACP, CHCQM
Chief Medical Officer
PDR