Major depressive disorder affects about 1 in 20 people yearly.¹ In a given year, 17.5 million American adults will experience depression.² Evidence suggests that the worldwide incidence of major depression is increasing.¹ Research and drug development over the past 15 years have provided expansive insight into the treatment of depression. The medical community has begun to see the true importance of recognizing and addressing this illness.

Behavioral Objectives Many of the most commonly dispensed medications are classified within the antidepressant category. Of the top 200 most prescribed medications of 1998, eight are classified as antidepressants. Of these eight antidepressants, three are within the top 15 most prescribed medications.³ This accounts for an enormous patient population that is encountered in our pharmacies on a regular basis. Compliance is very important with these medications to prevent relapse, since there is a temptation to discontinue therapy prematurely once symptoms of depression begin to subside. Therefore, providing education and encouragement to these patients can have a great impact on their therapeutic outcomes. Pharmacists are in an ideal position to provide necessary patient care, especially because of their regular contact with patients.

Major depression can affect anyone at any age, but commonly appears initially in people between the ages of 18 and 34 years.¹ In the United States the lifetime risk of suffering from major depressive disorder is 20% to 25% for women and 12% for men.⁴ Factors viewed as risks for depression are poor physical health, gender, chronic or malignant disease, old age, and drug or alcohol abuse.² The role of stress in inducing depression is still not well understood; however, chronic stress may precipitate depressive episodes.¹

Major depressive illness can cause an intense disability for afflicted patients, having a profound effect on their productivity and quality of life. It is estimated that the economic cost of depression ranges from $15 billion to $35 billion a year in lost productivity and medical care.² On an individual level, depression breaks down relationships, destroys careers, damages self-esteem, promotes alcohol and drug abuse, and can cause death.²

Depression is also a major risk factor for suicide. Approximately 15% of patients with unrecognized or inadequately treated depression will commit suicide.⁵ This is approximately 30 times the rate of occurrence in nondepressed patients.⁵ Depressed patients should be evaluated for their suicide potential, because adequate treatment reduces the risk of suicide and improves overall functioning and quality of life. Treatment includes accurate diagnosis and adequate dose and duration of antidepressant medications.⁵

There is strong evidence that major depression has a genetic component. Individuals who have parents or siblings with major depressive disorder have a 1.5 to 3 times increased risk of developing this disorder.⁴ Approximately, 8% to 18% of patients with major depression have at least one first-degree relative (father, mother, brother, or sister) with a history of depression.⁵ Children of biological parents who have depressive illness that are adopted and raised in a family where there is no depressive illness still have the same risk of developing a depressive disorder.⁴

The etiology of major depressive disorder is very complex, and despite the great progress that has been made in recent years, it is still not very well understood. A variety of factors appear to work together to cause or precipitate depressive syndromes.⁵ Genetics are believed to play a role in an individual’s ability to handle life’s unexpected events with or without developing a depressive disorder. However, patients with major depression have symptoms that reflect changes in brain chemistry—affecting norepinephrine, serotonin, and dopamine neurotransmitters.⁵ There are various hypotheses based on these neurotransmitters that attempt to describe the pathophysiology of depression.

The biogenic amine hypothesis places a reduction of the synaptic concentrations of norepinephrine and serotonin as the basis of depression. This has been postulated based on the mechanism of action of the antidepressants. Conversely, reserpine, an antihypertensive drug that depletes neuronal storage of norepinephrine, serotonin, and dopamine, induced clinically significant depression in at least 15% of treated patients.⁵ Reinforcement of this theory has been seen in healthy volunteers who develop depressive symptoms after dietary depletion of tryptophan, an essential amino acid that the body utilizes as a precursor to serotonin production.⁶

Photo of worried patient

The permissive hypothesis puts its emphasis on the neurotransmitter serotonin. This theory states that low levels of serotonin cause the expression of an affective disorder. The level of norepinephrine determines the type of affective state. When the norepinephrine levels are low, a depressive syndrome is induced. When the norepinephrine levels are high, a manic state is induced. To treat the affective disease, a correction of the low serotonin levels is necessary.⁵

The dysregulation hypothesis explains the origin of depression as a dysfunctional neurotransmitter system and an impairment of homeostatic mechanisms. This results in an erratic basal output of the neurotransmitter system—especially of serotonin—causing a disruption in the circadian rhythm and a less selective response to environmental stimuli. The impairment is not just related to the neurotransmitters but also to a reduction in receptor sensitivity.⁵

The majority of the hypotheses focus on the neurotransmitters, norepinephrine and serotonin. It has been suggested that dopamine neurotransmission may, at least in part, play a role in the mechanism of antidepressant drug action.⁵

One of the most perplexing observations in appropriately determining the origin of depression is the time difference between antidepressant drug action and the onset of clinical symptomatic improvement. In one research study, it was observed that the chronic administration of antidepressants to animals caused a desensitization or down-regulation of beta-adrenergic receptors. In studies of many of the antidepressants, this desensitization of the norepinephrine receptors corresponds to the time course of clinical effects of the antidepressants.⁵ Other studies have shown a similar down-regulation of serotonin receptors following chronic antidepressant administration.⁵

Research has provided substantial evidence that depression is an illness with a genetic origin and a documented pathophysiology. Unfortunately, although there has been extensive efforts to educate the public regarding the origin, diagnosis, and treatment of major depressive disorder, it is difficult to overcome the negative social stereotyping that surrounds the disorder. As a consequence, many depressed patients may not pursue professional medical attention. In addition, the symptoms of depression can prevent a person from seeking help. It is estimated that two thirds of people who have depression fail to seek treatment.² However, pharmacists are very accessible to the public, and it is likely that a depressed person may consult the advice of a pharmacist before any other health care professional.

Depression is a pervasive unhappiness that is associated with disturbances in a person’s ability to carry out their normal activities of daily living.¹ Depression varies in the degree and intensity of symptoms. In mild depression, some symptoms are present, but the individual is able to force themselves to carry out their daily activities. In moderate depression, many symptoms are evident keeping the individual from performing their daily activities. A severely depressed individual presents with nearly all the symptoms of depression and has difficulties coping with ordinary daily living.²

People are affected by depression in different ways. A depressed individual may not always appear depressed. The depressed person will likely suffer from dysphoria, or a mood disturbance. This depressed mood encompasses emotional symptoms such as feelings of sadness, emptiness, tearfulness, irritability, excessive guilt, worthlessness, helplessness, or hopelessness.¹ Changes in behavior are apparent and include decreased motivation and social withdrawal.² A depressed individual may experience anhedonia, which is the inability to feel normal emotions and the loss of interest in their usual activities.¹ Somatic complaints may include physical complaints without objective clinical findings, fatigue, decreased libido, sleep disturbances, and menstrual irregularities. Cognitive disturbances such as memory impairment, reduced ability to concentrate, and a decreased ability to carry out intellectual tasks may be encountered. A depressed person may also suffer from thoughts of self-harm or suicide. Symptoms of depression can vary with a person’s age and other aspects of their lives.²

The diagnostic criteria for major depressive episode are based on the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) and are listed in Table 1.⁷

Table 1. DSM-IV Criteria for Major Depressive Episode⁷

Table 1. DSM-IV Criteria for Major Depressive Episode

When a patient presents with depressive symptoms similar to those listed in the DSM-IV criteria, it is important to first consider possible medical or drug-induced causes. Patients coping with certain chronic medical conditions may experience depressive episodes during the course of their illness. Table 2 lists some physical illnesses and medications that may cause or precipitate a depressive episode.

Table 2. Organic Causes of Depression^1,4

Table 2. Organic Causes of Depression

Patients presenting with symptoms of depression should have a complete medical examination to assess the overall clinical picture of the patient. A physical and mental status examination and laboratory tests (including complete blood count with differential, thyroid function tests, and electrolyte determinations) will help to identify any existing medical problems. It is necessary to gather a complete patient history (including alcohol use) and obtain a thorough medication record (including over-the-counter [OTC] medication and herbal use).⁵ Other considerations for the reasons of depression may include current psychosocial situations, family history of depression, and any self-treatment the patient may have sought. The patient is a great source of information that may reveal potential contributing factors to the depressive state.

Depression can effectively be treated. Treatment includes medication and/or psychotherapy with a psychotherapist, psychologist, psychoanalyst, or counselor.² A combination of psychotherapy with antidepressant medication appears to have a synergistic effect.¹ With appropriate treatment, the symptoms of depression can be alleviated in approximately 80% of afflicted patients.² An untreated episode of depression in most patients will resolve on its own within 6 to 9 months.²

Approximately 70% to 80% of patients with major depressive disorder will respond to an antidepressant medication.¹ All antidepressant medications, when given in equipotent doses, are equally effective at treating depression. Therefore, selection of any agent is primarily made based on the side effects of the medications, patient characteristics, antidepressant use history, and pharmacogenetics (medications that have worked for other family members with depressive disorder).⁵

Considering the symptoms the patient is experiencing as a result of their depression can also aid in drug selection. For example, if the depression is causing insomnia, then the patient may benefit from the sedating properties of one of the antidepressant medications. There may be patient-specific issues that make one agent safer to use than another. For example, the orthostatic hypotension caused by many of the tricyclic antidepressants may make them less beneficial in the elderly, who are prone to falls—especially patients currently on antihypertensive medications, since such medications can enhance the side effects.

Generally, there are a few basic antidepressant principles that apply to all of the medications. There is a lag of 2 to 4 weeks to clinical efficacy for antidepressant medications, but the onset of side effects occurs rapidly. The delayed clinical response makes it difficult to establish the optimal dose or optimal drug immediately. An adequate dose and duration of treatment of at least 4 to 8 weeks are required to establish an adequate trial of an antidepressant. After this trial, an evaluation should be conducted. The patient should be reviewed for response, compliance, and possible adverse drug reactions.⁸

An antidepressant medication’s approximate time course to effect may occur in the following manner. The patient may, during the first few days of therapy, experience a reduction in agitation or anxiety. Within the initial 1 to 3 weeks, a gradually increasing improvement in sleeping patterns, appetite, mental concentration, and self-care should occur. After 2 to 4 weeks a relief of depressive feelings, a return of pleasure, and a decrease in suicidal thoughts should occur. It is proposed that the antidepressant dose should be increased if the patient compliance is good and there is no response after 3 weeks.⁸ If a partial response is achieved, then continue therapy for another 2 weeks prior to adjusting therapy.⁸

When the symptoms of depression are no longer present, a remission of the disease has been achieved. After this symptomatic recovery there is a period in which the patient is at a high risk of relapse. To prevent relapse, antidepressant medications should be continued for 6 to 9 months after remission. A recurrence is a separate episode of depression, which occurs after a period of time of normal functioning.⁵ One half of patients experiencing one depressive episode will experience a second.² There are patient characteristics that indicate a high probability of recurrence: persons less than 25 years or more than 50 years of age at the onset of their first episode; persons more than 40 years old with two or more prior episodes; persons of any age with three or more prior episodes.⁵ A patient may be a candidate for prophylactic treatment after the second or third depressive episode, or if the patient is considered a high risk for recurrence. There is no generally accepted time frame for the length of prophylactic treatment, and determinations are usually made on a case-by-case basis.⁸ Some patients may require lifelong treatment. Maintenance treatment is usually continued with the same antidepressant medication and at the same dose that brought about remission.⁸

Pharmacotherapy

Tricyclic Antidepressants

The tricyclic antidepressants (TCAs) are broken down into the tertiary amines (amitriptyline, clomipramine, doxepin, imipramine, trimipramine), and the secondary amines (desipramine, nortriptyline, and protriptyline). Amitriptyline and imipramine are the most extensively studied of the TCAs. When the secondary amines are compared to the tertiary amines, there is no difference in clinical efficacy. The secondary amines are more potent on a milligram-per-milligram basis, and the tertiary amines are generally less tolerated because of an increased incidence of anticholinergic effects, cardiotoxicity, and the impairment of memory and cognition. All TCAs enhance the activity of norepinephrine and serotonin by blocking their neuronal reuptake. The potency and selectivity of the TCAs vary among the agents.⁵ Because of their lack of specificity, the TCAs also affect other receptor systems and, therefore, are associated with anticholinergic, neurologic, and cardiovascular adverse effects.

Once the patients begin to respond to treatment, they may initially feel an increase in energy level while the symptoms of depression continue to persist. It is during this interim period that the risk of suicide is the greatest. The TCAs are the most toxic of the antidepressant medications available. A dose greater than 1 gram is toxic and can be fatal. Death occurs as a consequence of cardiac arrhythmias, hypotension, and seizures.¹ Patients who are at risk for suicide should be given small quantities, making sure that the patient does not have a large quantity of the drug in his possession at any one time. The pharmacist should be aware of any early refills that these at-risk patients make, and plan to counsel the patient, if needed.

The TCAs are metabolized via the cytochrome P-450 system in the liver. TCAs can increase the plasma levels of phenytoin and oral anticoagulants. Elevation in plasma concentrations of TCAs is seen with concurrent administration of cimetidine, phenothiazines, and selective serotonin reuptake inhibitors (SSRIs). Pharmacodynamically, the TCAs will potentiate the depressant effects of alcohol, enhance the anticholinergic effects of other drugs exhibiting anticholinergic activity, and decrease the antihypertensive effect of clonidine.⁵ There is a potential for numerous other drug interactions. It is advisable to monitor the patient’s drug regimen closely.

Maprotiline and amoxapine have a similar mechanism of action as the TCAs. Both of these drugs inhibit norepinephrine reuptake and have less of an effect on serotonin reuptake.⁵ Treatment with maprotiline is associated with causing seizures, sedation, and hallucinations.¹ Amoxapine, while less sedating, causes significant anticholinergic side effects. An active metabolite of amoxapine has dopamine-blocking activity; this activity causes extrapyramidal side effects, such as tardive dyskinesia, dystonia, pseudoparkinsonism, and akathisia.⁵

Selective Serotonin Reuptake Inhibitors

SSRIs have comparable efficacy to the TCAs, but also have a significantly improved safety and side- effect profile. The agents that are currently available are fluoxetine, sertraline, paroxetine, fluvoxamine, and citalopram. The distinguishing feature of these agents is that unlike the TCAs, they inhibit reuptake of serotonin into neurons to a much greater extent than they inhibit the reuptake of norepinephrine. The adverse effects associated with this drug class include nausea, anorexia, insomnia, headache, anxiety, agitation, and sexual dysfunction (delayed ejaculation, delayed orgasm, and anorgasmia).⁹ Some of these side effects may be transient in nature and subside within the first 1 to 2 weeks of therapy.

The SSRIs can inhibit enzymes in the cytochrome P-450 system, particularly fluoxetine. Samples of some of the drugs affected by this inhibition are the antiarrhythmics, anticoagulants, antipsychotics, neuroleptics, and the TCAs.⁵ Since the SSRIs can augment the effects of the TCAs when used concurrently, lower doses may be necessary, and the patient should be evaluated for toxicity.

Citalopram is the most recent SSRI to become available. Structurally it is unrelated to the other SSRIs, yet it is a highly selective serotonin reuptake inhibitor. Citalopram is a weak inhibitor of the cytochrome P-450 enzyme system. The CYP3A4 and CYP2C19 enzymes primarily metabolize citalopram; therefore, it is anticipated that potent inhibitors of the CYP3A4 enzyme (ketoconazole, itraconazole, and macrolide antibiotics) and potent inhibitors of the CYP2C19 enzyme (omeprazole) may decrease the clearance of citalopram.^10,11

Monoamine Oxidase Inhibitors

The monoamine oxidase inhibitors (MAOIs) increase the concentrations of serotonin, norepinephrine, and dopamine within the neuronal synapse because of their ability to inhibit the monoamine oxidase enzyme.⁵ The MAOIs—phenelzine, tranylcypromine, and isocarboxazid—have been shown to be most effective for treating a specific type of depression—atypical depression. Clinical features of atypical depression include mood reactivity, irritability, hypersomnia, hyperphagia, and psychomotor agitation.⁵
The difficulty with the MAOIs is the numerous dietary and medication restrictions that the patient must follow to avoid drug-food and drug-drug interactions. Hypertensive crisis can potentially occur when an MAOI is taken with foods high in tyramine (ie, aged cheeses, sour cream, yogurt, cottage cheese, wine, beer, herring, sardines, snails, anchovies, sauerkraut, coffee and chocolate [in large amounts], raisins, canned figs, fermented foods, and soy sauce). The symptoms of hypertensive crisis include occipital headache, stiff neck, nausea, vomiting, sweating, and elevated blood pressure.⁵ The hypertensive crisis is also seen when the MAOIs are taken with certain drugs (ie, amphetamines, appetite suppressants, asthma inhalants, cocaine, carbamazepine, methylphenidate, methyldopa, dopamine, dextromethorphan, ephedrine, decongestants [both topical and oral], cyclobenzaprine, and other antidepressants, such as maprotiline, SSRIs, bupropion, venlafaxine, and nefazodone).⁵ It is critical that patients prescribed MAOIs are educated about these dietary and drug interactions; an evaluation of MAOI usage should be made prior to recommending any OTC medication.

When two serotonergic agents are used together (eg, an SSRI and an MAOI), a resulting serotonin syndrome can occur. Symptoms of this syndrome include lethargy, restlessness, agitation, confusion, flushing, sweating, hypertension, rapid fluctuations of vital signs, and tremor. Therefore, SSRIs and MAOIs should not be used concurrently. When putting a patient on MAOI therapy after discontinuing SSRI therapy, it is recommended, prior to initiating the MAOI, to wait 6 weeks for fluoxetine and 2 weeks for the other SSRIs after discontinuation.¹

Bupropion

Bupropion is currently marketed as an antidepressant. It is a weak inhibitor of the neuronal reuptake of norepinephrine, serotonin, and dopamine. The risk for seizures with use of bupropion is greater than that with other antidepressant medications, therefore doses of more than 450 mg/day or more than 150 mg per dose are not recommended.¹² The most commonly encountered side effects are agitation, dry mouth, insomnia, headache, constipation, and tremor; bupropion does not commonly cause sexual dysfunction or sedation.¹

Trazodone

Trazodone works as an antidepressant by inhibiting serotonin reuptake and by acting as a serotonin antagonist. It is often used as a sleep aid, especially in patients taking other antidepressant medications that cause insomnia and agitation. The dosage for the treatment of depression is 200 to 600 mg/day, while the dose for insomnia is 25 to 100 mg/day. At higher doses, trazodone is not very well tolerated, since it can cause sedation, orthostatic hypotension, nausea, and vomiting, although nausea and vomiting can be minimized if the doses are taken with food. A rare reaction of trazodone is priapism, which is classified as a persistent and painful erection that can be irreversible and require surgery.⁵

Nefazodone

Nefazodone works by a dual mechanism of action, inhibiting serotonin reuptake and by blocking postsynaptic serotonin receptors. It has low to negligible affinity for cholinergic, histaminergic, or alpha1 adrenergic receptors. It is best to start with low doses (about 200 mg/day in divided doses) and slowly increase to desired clinical effect. Nefazodone can cause sedation, headache, dry mouth, and nausea; and nefazodone interacts with both triazolam and alprazolam. It is recommended that if alprazolam or triazolam is to be given concurrently with nefazodone, there should be a 50% to 75% reduction in the initial dose of alprazolam or triazolam, respectively. Furthermore, it is contraindicated to use nefazodone with any MAOI.⁵

Venlafaxine

Venlafaxine achieves its antidepressant effect by inhibiting reuptake of serotonin and norepinephrine. The most common side effects reported are nausea, constipation, dizziness, insomnia, nervousness, sweating, abnormal ejaculation or orgasm, and anorexia. Venlafaxine can cause dose-related increases in diastolic blood pressure; therefore, it is important to obtain a baseline blood pressure of the patient, to monitor it regularly, and to titrate doses upward slowly. If elevations in blood pressure occur, it may be necessary to reduce the patient’s dose. Venlafaxine is metabolized to an active metabolite by the cytochrome P-450 system. Drug interactions are expected to occur when venlafaxine is taken concurrently with any medication that inhibits this system.⁵

Mirtazapine

Mirtazapine has a very complex mechanism of action that involves increases in norepinephrine and antagonism of serotonin receptor sites. Reported adverse effects with mirtazapine, a substrate for the cytochrome P-450 enzyme system, include sedation, dizziness, increased appetite, and weight gain. In vitro studies have shown that mirtazapine is not a potent inhibitor of any of the enzymes, however, concomitant use of mirtazapine with other drugs metabolized by these enzymes has not been extensively studied.¹

Alternative Therapy

There has been an enormous amount of public interest involving herbal remedies to treat various medical conditions. One such herbal supplement, Hypericum perforatum, or St. John’s Wort, is being promoted for its antidepressant properties with few side effects (mild gastrointestinal effects, anxiety, and phototoxicity).⁶ Sunlight can cause a photosensitive reaction that can inflame the skin of light-skinned individuals, so patients taking St. John’s Wort should be cautioned about excessive exposure to sunlight.¹³

Various studies have shown St. John’s Wort to be an effective treatment for mild-to-moderate depression.¹ Controlled studies are currently being conducted. St. John’s Wort should not be taken by any woman who is planning a pregnancy, is pregnant, or is breast feeding. Concurrent use of St. John’s Wort with an SSRI or a MAOI has resulted in fever, confusion, and muscle spasms. The accepted dose is 300 mg three times daily of an extract standardized to 0.3% hypericin.¹³ In children 6 to 12 years of age, the dosage is 250 mg daily of the standardized product.¹⁴ St. John’s Wort should be taken with meals to avoid stomach discomfort.¹³ It may take 4 weeks of continuous treatment for St. John’s Wort to be effective.

It is important to encourage patients to report St. John’s Wort as part of their medication list to their physician and/or pharmacist. St. John’s Wort has the ability to increase the clearance of some drugs, consequently reducing their effectiveness—ie, oral contraceptives. For more information, the FDA has posted a list of medications that may be affected by St. John’s Wort. This list can be accessed at http://www.fda.gov/cder/ drug/advisory/stjwort.htm.¹⁵

Adverse Effects

Patients will have varying sensitivities to the effects and side effects of the antidepressant medications. These side effects may be of particular concern, because they may be the primary reason for noncompliance or drug discontinuance. Most often noncompliance or drug discontinuance leads to relapse, and patients begin to suffer again from the same symptoms of their depression. For this reason, patient education and monitoring is vital to successful drug treatment. The following are ideas for providing counseling, support, and possible drug alternatives when it is ascertained that side effects may be the cause of noncompliance.

Sexual dysfunction

Side effects, which include loss of erectile or ejaculatory function in men and loss of libido and anorgasmia in both sexes, are a more common consequence of therapy with the MAOIs, SSRIs, and venlafaxine. The lowest incidence is seen with bupropion. Sexual dysfunction may be a difficult topic for patients to discuss. Some therapeutic options are to reduce the dose or to change to another antidepressant, which possibly provides some relief. Bethanechol, cyproheptadine, or yohimbine can be added as adjunctive medication to improve sexual function.¹⁶ Prior to initiating any changes, an evaluation must be made to affirm that the sexual dysfunction is not the result of the underlying depression.

Anticholinergic effects

The most common undesirable side effects include dry mouth, blurred vision, urinary retention, constipation, and delirium. All of the TCAs have some degree of anticholinergic effects, but certain agents—amitriptyline, trimipramine, and amoxapine—have the highest incidence. Within this class, desipramine has the lowest potential of causing these side effects. The overall lowest incidence is seen with the SSRIs. Drugs with high potential to cause anticholinergic effects should be avoided in patients with benign prostatic hypertophy, glaucoma, or existing dementia.¹⁶

Dizziness/sedation

Dizziness may be the result of orthostatic hypotension caused by some of the antidepressant medications. Amitriptyline, doxepin, and trazodone are the agents most responsible for causing sedation, while nortriptyline and amoxapine are less sedating. Fluoxetine, sertraline, bupropion, protriptyline, and desipramine are the least sedating. Sedation may diminish after a few weeks of therapy. If the sedation poses a problem for the patient initially, consider encouraging them to continue therapy for a few weeks to see if the sedation subsides, or if possible, change to a bedtime dosage regimen.¹⁶

Weight loss/weight gain

Weight gain has been most problematic with the TCAs, MAOIs, and mirtazapine. In patients who are underweight or have difficulty gaining weight, these agents may be a good therapeutic choice. The SSRIs can cause transient and modest weight loss.¹⁶

Special Populations

Pregnancy

It is a generally accepted rule to avoid the use of medications in pregnancy whenever possible. However, pregnancy can be a time of increased vulnerability to depressive episodes. There is very limited information to guide treatment considerations for depression during pregnancy, and, because of obvious ethical reasons, drugs are not tested on pregnant women. What we know about how a medication may affect a developing embryo is primarily from data obtained from animal testing, or from women who may have been taking the medication when they became pregnant and who have remained on the medications throughout their pregnancy. It is known that the MAOIs are not safe to use during pregnancy. The TCAs have been used extensively during pregnancy. There has been no major teratogenic effects reported in women who have used TCAs during their pregnancy. Because of this finding, the TCAs are usually given preference in pregnancy—especially nortriptyline and desipramine. TCAs can cause both fetal and maternal withdrawal symptoms; therefore, it is advisable to slowly taper off the dose if the drug is to be discontinued. There is less information available regarding SSRI use in pregnancy, since there is less clinical experience because of their recent introduction to the market.^5,17

Elderly

Depression is a serious and prevalent disorder in the elderly population. It is estimated that approximately 15% of people more than 65 years of age experience depressive symptoms.² Depression in the elderly is responsible for high rates of suicide.¹⁸ Unfortunately, many elderly depressed patients are undiagnosed, because their depression is mistaken for another disorder (ie, dementia). Many of the typical complaints of the depressed patient, such as a depressed mood, are not common among depressed elderly patients. Instead, the depressed elderly patient may complain of a lack of appetite, insomnia, difficulty with memory, and may have physical complaints without substantial clinical findings.¹⁹ A thorough evaluation of medical conditions and current medication use are important to identify contributing factors of depression and to aid in appropriate drug therapy selection to treat the depression. When considering drug therapy, TCAs should be used cautiously because of their ability to cause sedative, anticholinergic, and cardiovascular side effects. Within the drug class, desipramine and nortriptyline have the lowest potential to cause anticholinergic side effects and may be the best therapeutic option. The SSRIs are generally considered the first choice for antidepressant therapy within the elderly population, because of their improved side- effect profile, which makes them safer and better tolerated.^5,16

Conclusions

Major depressive disorder has been described as a major public health problem. The disorder has a devastating effect on a person’s ability to work and their quality of life—limiting their functioning at both the physical and personal levels. Consequently, their families, communities, and coworkers are considerably affected by their depression. Recent research developments have provided evidence that depression is a disorder of brain chemistry, and experience with the disorder has provided a strong correlation for a genetic component to the disorder. As a consequence, drug therapies have been developed that successfully treat the disorder. In fact, because of the availability of novel antidepressant compounds, pharmacologic intervention has become the cornerstone for treatment of depression. Despite these advancements, depression still remains underdiagnosed and undertreated. The tendency to underestimate the importance and prevalence of depression may be the result of the social stigma that is often associated with the disorder. The pharmacist has a duty to educate the public to dispel the myths regarding depression. The pharmacist must be knowledgeable about available drug therapies to advise the physicians and/or patients on drug selection and alternatives and to be able to tailor therapy to the needs of each individual patient. The pharmacist also has a responsibility to monitor the patient currently on therapy to ensure compliance and tolerability with the current drug therapy regimen. The pharmacist who has an understanding of the symptoms associated with depression can have a vital impact on the disorder’s recognition and play a role in ameliorating a very treatable disorder.

References

1. McMurray J. Clinical Reviews. Micromedex Healthcare Series. 2000 Vol. 104.

2. American Medical Association. Essential Guide to Depression. New York, NY: Pocket Books; 1998:11-33.

3. The Top 200 Prescriptions of 1999. American Druggist February 1999;42-43.

4. Long WL. Major Depressive Disorder American Description. [web page] Oct 1996; http://mentalhealth.com/dis1/p21-md01.html. [Accessed 10 Jun 2000].

5. Wells BG, Mandos LA. Depressive Disorders. In: Dipiro JT, Talbert RL, Yee GC, Matzke GR, Wells BL, Posey LM, eds. Pharmacotherapy: A Pathophysiologic Approach, Third Edition. Stamford, Connecticut: Appleton and Lange; 1997:1395-1417.

6. Doris A, Ebmeier K, Shajahan P. Depressive illness. Lancet. 1999;354(9187):1369-1375.

7. American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. Washington, DC: American Psychiatric Association, 1994.

8. Spigset O, Martensson B. Fortnightly review: Drug treatment of depression. British Medical Journal. 1999;318(7192):1188-1191.

9. Gram LF. Drug Therapy: Fluoxetine. The New England Journal of Medicine. 1994;331(20):1354-1361.

10. Celexa Package Insert. Forest Pharmaceuticals, Inc. 2000

11. Willets J, Lippa, A, Beer B. Clinical Development of Citalopram. Journal of Clinical Psychopharmocology. 1999;19(5)36S-46S.

12. Wellbutrin Package Insert. GlaxoWellcome. 1999

13. Pelletier KR. The Best Alternative Medicine. New York, NY: Simon and Schuster; 2000:169,344.

14. Jonas WB, Levin JS. Essentials of Complementary and Alternative Medicine. Philadelphia, Pa: Lippincott Williams and Wilkins; 1999:360-61.

15. Rosenfeld I. St. John’s Wort- A Mismatch with Some Drugs. Parade Magazine. May 28, 2000:11.

16. Practice Guidelines for Major Depressive Disorder in Adults. American Journal of Psychiatry. 1993;150(4).

17. Wisner KL, Gelenberg AJ, Leonard H, Zarin D, Frank E. Pharmacologic Treatment of Depression During Pregnancy. JAMA. 1999;282(13):1264-1269.

18. Cole MG, Bellavance F, Mansour A. Prognosis of Depression in Elderly Community and Primary Care Populations. American Journal of Psychiatry. 1999;156(8):1182-1189.

19. Hale AS. ABC of mental health: Depression. British Medical Journal. 1997;315(7099):43-46.

Introduction | References

Temple University School of Pharmacy is approved by the American Council on Pharmaceutical Education (ACPE) as a provider of continuing pharmaceutical education. Its CE programs are developed in accordance with the “Criteria for Quality and Interpretive Guidelines” of ACPE. This program is acceptable for 2.0 hours of Continuing Education Credits (0.2 CEU) through August 31, 2003. ACPE Pgm I.D. 057-999-00-055-H01.

Major Depressive Disorder

Jennifer Ann Kubiak, BS, RPh, PharmD Candidate

Table 1. DSM-IV Criteria for Major Depressive Episode7

Table 2. Organic Causes of Depression1,4

Sexual dysfunction

Weight loss/weight gain

Introduction | References

Table 1. DSM-IV Criteria for Major Depressive Episode⁷

Table 2. Organic Causes of Depression^1,4