Table 15.

1-36 Antidepressant Medications Usual Daily Generic Dose (Brand) Name (mg) Common Side Effects Clinical Caveats NE Reuptake Inhibitors Desipramine 75-300 Drowsiness, insomnia, Overdose may be fatal. Dose titration is (Norpramin, OSH, agitation, CA, weight needed. Pertofrane) up ,anticholinergica Protriptyline (Vivactil) 20-60 Drowsiness, insomnia, OSH, agitation, CA, anticholinergica Overdose may be fatal. Dose titration is needed.

Nortriptyline (Aventyl, Pamelor) Maprotiline (Ludiomil)

40-200 Drowsiness, OSH, CA, Overdose may be fatal. Dose titration is weight up ,anticholinergica needed.

100-225 Drowsiness, CA, weight up Overdose may be fatal. Dose titration is ,anticholinergica needed.

5-HT Reuptake Inhibitors Citalopram 20-60 All SSRIs may cause (Celexa) insomnia, agitation, Escitalopram 10-20 sedation, GI distress, and (Lexapro) sexual dysfunction Fluoxetine 10-40 (Prozac) Fluvoxamine 100-300 (Luvox)b Paroxetine 20-50 (Paxil) Sertraline 50-150 (Zoloft) NE and 5-HT Reuptake Inhibitors Amitriptyline 75-300 Drowsiness, OSH, CA, (Elavil, Endep) weight up ,anticholinergica Doxepin (Triadapin, Sinequan) Imipramine (Tofranil)

Many SSRIs inhibit various cytochrome P450 isoenzymes. They are better tolerated than tricyclics and have high safety in overdose. Shorter half-life SSRIs may be associated with discontinuation symptoms when abruptly stopped.

Overdose may be fatal. Dose titration is needed.

75-300 Drowsiness, OSH, CA, Overdose may be fatal a weight up ,anticholinergic

Trimipramine (Surmontil) Venlafaxine (Effexor)

75-300 Drowsiness, insomnia and Overdose may be fatal. Dose titration agitation, OSH, CA, GI needed. distress, weight up ,anticholinergica 75-300 Drowsiness, OSH, CA, weight up ,anticholinergica 150-375 Sleep changes, GI distress,Higher doses may cause hypertension. discontinuation syndrome Dose titration is needed. Abrupt

discontinuation may result in discontinuation symptoms. Duloxetine (Cymbalta) 30-60 GI distress, discontinuation syndrome

Pre- and Postsynaptic Active Agents Nefazodone 300-600 Sedation Mirtazapine (Remeron) 15-30 Sedation, weight

Dose titration is needed. No sexual dysfunction. No sexual dysfunction.

Dopamine Reuptake Inhibitor Bupropion 200-400 Insomnia or agitation, GI (Wellbutrin) distress Mixed Action Agents Amoxapine 100-600 Drowsiness, (Asendin) insomnia/agitation, CA, weight up ,OSH, anticholinergica Clomipramine (Anafranil) 75-300 Drowsiness, weight

Twice-a-day dosing with sustained release. No sexual dysfunction or weight gain.

Movement disorders may occur. Dose titration is needed.

Dose titration is needed.

Trazodone 150-600 Drowsiness, OSH, CA, GI Priapism is possible. (Desyrel) distress, weight Note: Dose ranges are for adults in good general medical health, taking no other medications, aged 18 to 60 years. Doses vary depending on the agent, concomitant medications, the presence of general medical or surgical conditions, age, genetic constitution, and other factors. Brand names are those used in the United States. CA, cardiac arrhythmia; 5-HT, serotonin; GI, gastrointestinal; NE, norepinephrine; OSH, orthostatic hypotension; SSRI, selective serotonin reuptake inhibitor. a Dry mouth, blurred vision, urinary hesitancy, and constipation. b Not approved as an antidepressant in the United States by the US Food and Drug Administration.

ANTIDEPRESSANT MEDICATIONS About half of moderate-to-severe episodes of depression will improve with antidepressant treatment. Classes of antidepressant agents are defined by their mechanism of action (Table 1TABLE 1Classification, Doses, Safety, and Side Effects of Antidepressants.). Many agents with effective antidepressant action amplify serotonin or norepinephrine signaling by inhibiting

reuptake at the synaptic. The several classes of drugs include SSRIs, norepinephrine-reuptake inhibitors, and dual-action agents that inhibit uptake of serotonin and norepinephrine. Monoamine oxidase inhibitors (MAOIs) inhibit monoamine degradation by monoamine oxidase A or B. Other antidepressant agents antagonize 2adrenergic autoreceptors with a resultant increase in the release of norepinephrine, antagonize 5-hydroxytryptamine2A (5-HT2A) receptors, or both 1. SSRIs Clinical trials have shown little difference in efficacy or tolerability among various available SSRIs or between SSRIs and other classes of antidepressants. However, some specific differences should be noted. The active metabolite of fluoxetine has a half-life that is longer than that of other SSRIs, which permits once-daily dosing and thereby reduces the effect of missed doses and mitigates the SSRI discontinuation syndrome (described below). However, fluoxetine should be used with caution in patients with bipolar disorder or a family history of bipolar disorder, because an active metabolite persists for weeks and may aggravate the manic state in the event of a switch from depression to mania. At higher doses, paroxetine and sertraline also block dopamine reuptake, which may contribute to their antidepressant action. SSRIs can be helpful in patients who do not have a response to tricyclic antidepressants, an older class of drugs, and appear to be better tolerated with lower rates of discontinuation and fewer cardiovascular effects. Although tricyclic antidepressants may have greater efficacy than SSRIs in severe major depressive disorder or depression with melancholic features, they are less effective than SSRIs for bipolar depression, since they can trigger mania or hypomania. SSRIs appear to be less effective than either tricyclic antidepressants or selective norepinephrine-reuptake inhibitors for depression in which physical symptoms or pain is prominent. The SSRI fluoxetine is the only antidepressant that has consistently been shown to be effective in children and adolescents, and SSRIs may be superior to selective norepinephrine-reuptake inhibitors in young adults (18 to 24 years of age), although they are more likely to trigger mania in children. 2. Norepinephrine-Reuptake Inhibitors Nortriptyline, maprotiline, and desipramine are tricyclic norepinephrine-reuptake inhibitors with anticholinergic effects Reboxetine is a selective norepinephrine-reuptake inhibitor with an effectiveness similar to that of tricyclic antidepressants and SSRIs, though it is unavailable in the United States.

3. Dual-Action Antidepressants Serotoninnorepinephrine reuptake inhibitors such as venlafaxine, duloxetine, and milnacipran block monoamine transporters more selectively than tricyclic antidepressants and without the cardiac-conduction effects that can occur with tricyclic agents. Some tricyclics (imipramine and amitriptyline) inhibit both serotonin and norepinephrine reuptake. The dual-action antidepressant venlafaxine appears to demonstrate superior efficacy and higher rates of remission in severe depression as compared with either SSRIs such as fluoxetine or tricyclic antidepressants. The efficacy of duloxetine is similar to that of the SSRI paroxetine. Venlafaxine and duloxetine are effective for the treatment of chronic pain and diabetic neuropathic pain, respectively,1 as well as pain occurring as part of primary or secondary depression. Bupropion, which inhibits both norepinephrine and dopamine reuptake, has no direct action on the serotonin system and is generally similar in efficacy to tricyclic antidepressants and SSRIs. Bupropion is associated with less nausea, diarrhea, somnolence, and sexual dysfunction than are SSRIsand constitutes an effective alternative, or adjunctive therapy, for patients who do not have a response to SSRIs 4. MAOIs Older, irreversible MAOIs nonselectively block MAO A and B isoenzymes and have an antidepressant efficacy similar to that of tricyclic antidepressants. However, MAOIs are not firstline drugs because patients who receive them must adhere to a low-tyramine diet to prevent hypertensive crisis and because MAOIs carry greater drug-interaction risks than do other medications. MAOIs appear to be superior to tricyclic agents for people with depression characterized by extreme fatigue or extreme psychological sensitivity to rejection or failed relationships. MAOIs are also useful for treating patients who do not have a response to tricyclic antidepressants. The reversible selective MAO A inhibitor moclobemide (which is not available in the United States but widely available in other countries) and the MAO B-selective inhibitor, selegiline, have a greater safety margin than do SSRIs but similar efficacy A selegiline transdermal patch is under consideration by the Food and Drug Administration (FDA). AUGMENTING AND ADJUNCTIVE MEDICATIONS Various medications used in conjunction with other antidepressants may help to augment the effect of antidepressants . They can also target different components of patients' symptoms (such as delusions) or help to prevent a switch into mania. Mood Stabilizers

Lithium is an antimanic agent and, as a mood stabilizer, prevents the recurrence of mania or depression

Antipsychotic Agents

Typical antipsychotic agents (e.g., chlorpromazine, fluphenazine, and haloperidol) block the dopamine D2 receptor, whereas atypical antipsychotic agents (e.g., clozapine, olanzapine, risperidone, quetiapine, ziprasidone, and aripiprazole) TALK THERAPY Talk therapy is counseling to talk about your feelings and thoughts, and help you learn how to deal with them. Types of talk therapy include:

Cognitive behavioral therapy teaches you how to fight off negative thoughts. You will learn how to become more aware of your symptoms and how to spot things that make your depression worse. You'll also be taught problem-solving skills. Psychotherapy can help you understand the issues that may be behind your thoughts and feelings. Joining a support group of people who are sharing problems like yours can also help. Ask your therapist or doctor for a recommendation. OTHER TREATMENTS FOR DEPRESSION Electroconvulsive therapy (ECT) is the single most effective treatment for severe depression and it is generally safe. ECT may improve mood in people with severe depression or suicidal thoughts who don't get better with other treatments. It may also help treat depression in those who have psychotic symptoms. Transcranial magnetic stimulation (TMS) uses pulses of energy to stimulate nerve cells in the brain that are believe to affect mood. There is some research to suggest that it can help relieve depression. Light therapy may relieve depression symptoms in the winter time. However, it is usually not considered a first-line treatment.