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 The leading web portal for pharmacy resources, news, education and careers March 21, 2018
Pharmacy Choice - Depression Disease State Management - March 21, 2018

Depression Disease State Management

Focus on Pharmacotherapy for Depression
by Darrell Hulisz, RPh, PharmD
Associate Professor of Family Medicine
Case Western Reserve University, School of Medicine

Each year approximately 21 million Americans suffer a major depressive episode, or about 16% of the population. The lifetime prevalence of depression in women is 10-25% and 5-12% for men. First-degree relatives of patients with depression are 1.5-3 times more likely to develop depression. Unfortunately, up to 15% of depressed patients will attempt suicide; thus, prompt recognition and effective treatment for depression is critical. In addition to suicidal ideation, other symptoms of depression include anhedonia (loss of interest in pleasurable activities), feelings of guilt and hopelessness, decline in energy and appetite, difficulty concentrating, psychomotor changes and insomnia.

The exact pathogenesis and etiology of depression is unknown, and cannot be explained by a single sociological, developmental, or biological theory. Dysregulation of neurotransmitter systems, such as serotonin and norepinephrine are likely to be involved. Other neurotransmitters implicated include dopamine, glutamate, and brain-derived neurotrophic factor. Some medications may exacerbate and even induce depression in susceptible individuals. This includes centrally-acting antihypertensives, such as clonidine, reserpine, methydopa, varenicline, corticosteroids, interferons, and CNS depressants. Psychosocial risk factors for depression may also play a role, especially for depression that develops later in life. Such factors include impaired social supports, caregiver burden, loneliness, bereavement, and adverse life events.

Patients who are depressed often initially receive non-pharmacological treatment, with or without medications. Examples include cognitive-behavioral therapy, interpersonal therapy, psychoanalysis, family therapy, insight training, light therapy (for seasonal affective disorder) and electroconvulsant therapy (for refractory cases). Additionally patients should use self-help techniques, support groups, prayer, meditation, aerobic exercise and relaxation methods as part of a comprehensive approach to treating depression. Most patients with depression will also need pharmacotherapy for effective treatment. A wide variety of antidepressant classes are available. These include tricyclic antidepressants (e.g. amitriptyline), selective serotonin-reuptake inhibitors (SSRI) (e.g. fluoxetine), selective serotonin-norepinephrine reuptake inhibitors (SNRI) (e.g. venlafaxine), mixed agents (e.g. bupropion), atypical agents (e.g. mirtazapine), and MAO-inhibitors (e.g. phenylzine). Over-the-counter agents and natural products have not been proven to be efficacious for major depression in large-scale, randomized, placebo controlled trials. However, St. John's Wort has shown positive results in some studies of mild depression. The use of St. John's Wort for depression should be medically supervised because of the risk of suicide exists, as does the potential for other underlying disorders to emerge that can mimic depression. Furthermore, St. John's Wort is a potent inducer of Cytochrome P450-3A4 enzyme. Numerous drug interactions are possible since this is a common pathway for drug metabolism.

There are no evidence-based guidelines exist to predict the ideal initial antidepressant drug. However, general principles can be followed, such as consideration of a patient's history of response, if applicable. A history of familial antidepressant response may also be helpful. A patient's concurrent medical history, presenting symptoms, potential for drug interactions, cost, and adverse reaction profile should also be taken into account. Most experts agree that efficacy of different antidepressants is generally comparable across and within classes. Pharmacotherapy plus psychotherapy, rather than pharmacotherapy alone is preferred in most patients with depression. Treatment with an antidepressant is generally initiated with an SSRI. However, SNRIs, atypical antidepressants, and bupropion are reasonable alternatives. Tricyclic antidepressants and monoamine oxidase inhibitors are typically not prescribed as initial treatment because of safety concerns and adverse effects. For example, tricyclic antidepressants are highly lethal in overdose and should not be prescribed for patients who are actively suicidal.

A minority of patients may experience partial response to antidepressant treatment within the first two weeks. However, most patients will require a periods of six weeks or longer to respond to therapy, during which time dosages are often titrated upward as tolerated. The duration of continuation pharmacotherapy is typically six months; however, patients with risk factors for recurrence should receive one to three years of maintenance treatment following continuation treatment. Longer periods of maintenance therapy may decrease the likelihood of a major depressive episode relapse.

Pharmacists should counsel patients with depression about the lag time seen between the start of drug therapy and a positive therapeutic response, which can be as long as four to six weeks. Patients should be encouraged to remain adherent to medications during this initial period and should report any adverse reactions to their physician. Pharmacists should encourage patients to be adherent with counseling and behavioral treatment if prescribed, including supportive treatment such as exercise. Monitoring for antidepressant efficacy would include asking patients if depressive symptoms are improving. Pharmacists can easily recall these symptoms with the pneumonic SIGECAPS (Sleep disturbance, Interest decline, Guilt feelings, Energy decline, Concentration difficulty, Appetite decline, Psychomotor changes, Suicide ideation). Patients who reveal suicidal thoughts should be triaged for emergency medical and psychiatric management.
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