A Generalist's Guide to Treating Patients With Depression With an Emphasis on Using Side Effects to Tailor Antidepressant Therapy
2010; Elsevier BV; Volume: 85; Issue: 6 Linguagem: Inglês
10.4065/mcp.2009.0565
ISSN1942-5546
Autores Tópico(s)Schizophrenia research and treatment
ResumoThis review provides a guide to the primary care physician for diagnosing and managing depression. To identify relevant articles, a PubMed search (ending date parameter, October 15, 2009) was conducted using the keywords depression, antidepressants, side effects, adverse effects, weight gain, sexual dysfunction, and sleep disturbance, and the reference lists of relevant articles were hand searched. This review explores the challenges in diagnosing depression that will and will not respond to antidepressants (ADs) and describes the value of 2-question screening instruments followed by in-depth questioning for positive screening results. It underscores the implications of veiled somatic presentations in which underlying depression is missed, leading to fruitless and expensive medical work-ups. Following this survey of the difficulties in diagnosing depression, the 4 options generalists have for treating a patient with depression are discussed: watchful waiting, antidepressant therapy, psychotherapy, and psychiatric referral. This review proposes that physicians, once they decide to prescribe, use AD side effects to advantage by selecting medications to minimize negative and maximize positive possibilities, thereby improving adherence. It focuses on the 3 most troubling adverse effects—sleep disturbance, sexual dysfunction, and weight gain. It provides AD-prescribing principles to assist primary care physicians in successfully managing depression and appropriately referring patients to a psychiatrist. Antidepressant therapy is not a panacea for treating patients with depression. An approach blending enlightened observation, medications, and psychotherapy often helps depressed patients recover to their former baselines. This review provides a guide to the primary care physician for diagnosing and managing depression. To identify relevant articles, a PubMed search (ending date parameter, October 15, 2009) was conducted using the keywords depression, antidepressants, side effects, adverse effects, weight gain, sexual dysfunction, and sleep disturbance, and the reference lists of relevant articles were hand searched. This review explores the challenges in diagnosing depression that will and will not respond to antidepressants (ADs) and describes the value of 2-question screening instruments followed by in-depth questioning for positive screening results. It underscores the implications of veiled somatic presentations in which underlying depression is missed, leading to fruitless and expensive medical work-ups. Following this survey of the difficulties in diagnosing depression, the 4 options generalists have for treating a patient with depression are discussed: watchful waiting, antidepressant therapy, psychotherapy, and psychiatric referral. This review proposes that physicians, once they decide to prescribe, use AD side effects to advantage by selecting medications to minimize negative and maximize positive possibilities, thereby improving adherence. It focuses on the 3 most troubling adverse effects—sleep disturbance, sexual dysfunction, and weight gain. It provides AD-prescribing principles to assist primary care physicians in successfully managing depression and appropriately referring patients to a psychiatrist. Antidepressant therapy is not a panacea for treating patients with depression. An approach blending enlightened observation, medications, and psychotherapy often helps depressed patients recover to their former baselines. The lifetime risk of developing major depressive disorder in the United States is 16.2%, making it among the most common conditions physicians encounter.1Kessler RC Berglund P Demler O et al.The epidemiology of major depressive disorder: results from the National Comorbidity Survey Replication (NCS-R).JAMA. 2003; 289: 3095-3105Crossref PubMed Scopus (6330) Google Scholar Up to 10% of outpatients treated by generalists meet criteria for major depression.2Williams Jr, JW Competing demands: does care for depression fit in primary care?.J Gen Intern Med. 1998; 13: 137-139Crossref PubMed Scopus (54) Google Scholar Yet primary care physicians have an abysmal record of inquiring about depression. In a survey of patients with chronic or recurrent depression, family practice physicians asked about depressive symptoms only 34.0% of the time and internists only 27.3% of the time.3Nichols GA Brown JB Following depression in primary care: do family practice physicians ask about depression at different rates than internal medicine physicians?.Arch Fam Med. 2000; 9: 478-482Crossref PubMed Scopus (16) Google Scholar In a nationally representative survey, only 41.9% of depressed patients reported receiving adequate treatment for their depression from their primary care physicians.4Dietrich AJ Oxman TE Williams Jr, JW Treatment of depression by mental health specialists and primary care physicians [letter].JAMA. 2003; 290: 1991Crossref PubMed Scopus (4) Google Scholar For treatment of major depressive disorder, generalists currently have watchful waiting, initial psychopharmacological treatment, psychotherapy, and psychiatric referral in their armamentarium. This review surveys these management options, emphasizing the most problematic adverse effects associated with the use of antidepressants (ADs) and offering suggestions—if medication is indicated—on how to tailor a side-effect profile to a particular patient's presentation. It offers parameters within which to define appropriate treatment length and other principles for prescribing ADs. Finally, it provides specific guidance on when to recommend psychotherapy and when to refer the patient to a psychiatrist. To identify relevant articles for this review, a PubMed literature search (ending date parameter, October 15, 2009) was conducted using the keywords depression, antidepressants, side effects, adverse effects, weight gain, sexual dysfunction, and sleep disturbance, and reference lists in the identified articles were hand searched for additional relevant publications. Major depression is described as "a heterogenous disorder with a highly variable course, an inconsistent response to treatment, and no established mechanism."5Belmaker RH Agam G Major depressive disorder.N Engl J Med. 2008; 358: 55-68Crossref PubMed Scopus (1331) Google Scholar Adding to its protean complexity are its multiple symptom domains (eg, emotional, somatic, and behavioral), which may be variably expressed in conjunction with dysregulation of appetite, sleep, energy, and concentration.6Gelenberg AJ Hopkins HS Assessing and treating depression in primary care medicine.Am J Med. 2007; 120: 105-108Abstract Full Text Full Text PDF PubMed Scopus (31) Google Scholar When somatization is particularly prominent, as it is in two-thirds of depressed patients presenting to primary care, blindsided physicians may focus on working up physical symptoms and fail to probe for their depressive underpinnings. This is a primary reason why generalists miss the depression diagnosis.7Timonen M Liukkonen T Management of depression in adults.BMJ. 2008; 336: 435-439Crossref PubMed Scopus (53) Google Scholar Conversely, much of what at first glance looks like major depression may turn out with further examination to fit criteria for another entity, such as adjustment disorder, bereavement, cognitive disorder, personality style, or dysthymia (Table 1). The first 2 entities either fail to rise to the level of major depression or have not been present long enough to meet criteria. The third and fourth entities are characterized by patterns of interacting with the world that have become pervasive rather than episodic. The last, a chronic form of mild depression, consists of depressed mood and 2 or more depressive symptoms present for at least 2 years. If a patient lacks a medical or psychiatric comorbid condition, a physician should be even more reluctant to assume the presence of major depression. In a Finnish sample of 137 patients with major depression, only 12% had neither additional psychiatric diagnoses nor chronic physical illness. The investigators concluded that "treatment of depression in primary care should not rest on an assumption of short-lived, uncomplicated mild disorders."9Vuorilehto M Melartin T Isometsa E Depressive disorders in primary care: recurrent, chronic, and co-morbid.Psychol Med. 2005; 35: 673-682Crossref PubMed Scopus (85) Google ScholarTABLE 1Differential Diagnosis of Depressive Syndromes Depressive symptoms 1.Depressed mood2.Decreased pleasure3.Weight loss or weight gain4.Insomnia or hypersomnia5.Psychomotor agitation or retardation6.Fatigue or reduced energy7.Preoccupation with feelings of worthlessness or guilt8.Poor concentration or indecisiveness9.Morbid or suicidal thoughts10.Substantial social or occupational impairmentMajor depressive disorder Either 1 or 2; at least 4 items from 3-9 for at least 2 wk; 10Dysthymia 1; at least 2 items from 2-9 for at least 2 y; 10Adjustment disorder with depressed mood Identifiable stressor but symptoms out of proportion to what is expectedNot enough symptoms to meet major depressive disorder criteriaSubstantial social or occupational impairmentStressor within 3 mo, impairment not longer than 6 moBereavement Specific stressor: death of a loved oneSymptoms resemble major depressive disorder, but patient considers them appropriateMajor depressive disorder diagnosis is not given unless symptoms persist longer than 2 mo or include guilt not related to the dead, a preoccupation with worthlessness, marked psychomotor retardation, suicidal ideation, and prolonged and marked functional impairmentFrom Quick Reference to the Diagnostic Criteria From DSM-IV-TR,8American Psychiatric Association Quick Reference to the Diagnostic Criteria From DSM-IV-TR®. American Psychiatric Association, Arlington, VA2000: 167-208Google Scholar with permission. Open table in a new tab From Quick Reference to the Diagnostic Criteria From DSM-IV-TR,8American Psychiatric Association Quick Reference to the Diagnostic Criteria From DSM-IV-TR®. American Psychiatric Association, Arlington, VA2000: 167-208Google Scholar with permission. Major depression is strictly a clinical diagnosis made on clinical grounds. Initial screening is easily accomplished with a 2-question case-finding instrument, the Patient Health Questionnaire 2, which has proven as effective as much more complex instruments in establishing the diagnosis. With their references to time frame, depressed mood, and anhedonia, the 2 queries contain the sine qua non criteria for establishing the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition, Text Revision) diagnosis: "During the past month, have you often been bothered by feeling down, depressed, or hopeless?" and "During the past month, have you often been bothered by little interest or pleasure in doing things?" Positive answers to both are associated with a sensitivity of 96% and a specificity of 57%.10Whooley MA Avins AL Miranda J Browner WS Case-finding instruments for depression: two questions are as good as many.J Gen Intern Med. 1997; 12: 439-445Crossref PubMed Scopus (1357) Google Scholar, 11Arroll B Khin N Kerse N Screening for depression in primary care with two verbally asked questions: cross sectional study.BMJ. 2003; 327: 1144-1146Crossref PubMed Scopus (391) Google Scholar Negative answers to both make clinically relevant depression unlikely and alternative diagnoses more likely.12Williams Jr, JW Noel PH Cordes JA Ramirez G Pignone M Is this patient clinically depressed?.JAMA. 2002; 287: 1160-1170Crossref PubMed Scopus (267) Google Scholar Having screened positive on at least 1 of the 2 items in the case-finding instrument, patients should be asked additional questions to see whether they meet the major depression threshold, particularly because 2-question instruments identify 8 of 10 cases of depression but have a false-positive rate of 60%.13Mitchell AJ Coyne JC Do ultra-short screening instruments accurately detect depression in primary care? a pooled analysis and meta-analysis of 22 studies.Br J Gen Pract. 2007; 57: 144-151PubMed Google Scholar Endorsement of at least 4 more symptoms for at least 2 weeks along with social and occupational impairment is required to make the diagnosis (Table 1). In managing suspected depression, the generalist has 4 treatment options: watchful waiting, psychopharmacological treatment, psychotherapy, and referral to a psychiatrist. The vigorous marketing of ADs and the availability of more than 2 dozen of them on the US market may encourage physicians to opt for psychopharmacological therapy, but even in this age of the "Prozac Nation," reflexively prescribing an AD on flimsy grounds is certainly contraindicated. An initial, more conservative approach of watchful waiting may be appropriate. With adverse effects of ADs common and prescription costs high, Ackermann and Williams14Ackermann RT Williams Jr, JW Rational treatment choices for non-major depressions in primary care: an evidence-based review.J Gen Intern Med. 2002; 17: 293-301Crossref PubMed Scopus (65) Google Scholar favor watchful waiting with frequent face-to-face contact to assess whether symptoms have resolved or more aggressive treatment is indicated. Ackermann and Williams14Ackermann RT Williams Jr, JW Rational treatment choices for non-major depressions in primary care: an evidence-based review.J Gen Intern Med. 2002; 17: 293-301Crossref PubMed Scopus (65) Google Scholar note the tendency of primary care physicians to prescribe ADs reflexively for what they label minor depression, ie, depressive syndromes that fail to rise to the standard of 4 or more distinct symptoms beyond depressed mood and anhedonia. A scanty literature does not support AD efficacy in this population. The physician's judgment about whether symptoms will spontaneously resolve in 2 to 4 weeks should determine whether medication is prescribed.10Whooley MA Avins AL Miranda J Browner WS Case-finding instruments for depression: two questions are as good as many.J Gen Intern Med. 1997; 12: 439-445Crossref PubMed Scopus (1357) Google Scholar Other diagnoses for which ADs are inappropriate are normal bereavement and adjustment disorders, which by definition cannot meet criteria for another acute depressive or anxiety disorder. "Current data suggest that clinicians should consider active treatment only for those individuals with more severe functional impairment," these psychotropic minimalists opine, recommending "[a] 4-to-8 week trial of support, education, and when appropriate, exercise, … for all others."14Ackermann RT Williams Jr, JW Rational treatment choices for non-major depressions in primary care: an evidence-based review.J Gen Intern Med. 2002; 17: 293-301Crossref PubMed Scopus (65) Google Scholar Despite a burgeoning literature purporting to show the therapeutic efficacy of AD medications, prescribers will do well to proceed with appropriate skepticism. First, AD response, defined as a 50% reduction in depressive symptoms, is not the same as depression remission. Only about a third of patients achieve full symptom resolution after 3 months of treatment with an initial AD, and only two-thirds achieve full remission, even after trials of 3 additional ADs.15Rush AJ Trivedi MH Wisniewski SR et al.Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report.Am J Psychiatry. 2006; 163: 1905-1917Crossref PubMed Scopus (1904) Google Scholar Second, by the time several ADs have been tried, the episode might be expected to resolve on its own. In the Baltimore Epidemiological Catchment Area Study, the median length of a first depressive episode was 20 weeks, with subsequent episodes typically somewhat shorter. Only half of the first-episode group had a recurrence during 15 years of follow-up.16Eaton WW Shao H Nestadt G Lee HB Bienvenu OJ Zandi P Population-based study of first onset and chronicity in major depressive disorder.Arch Gen Psychiatry. 2008; 65: 513-520Crossref PubMed Scopus (417) Google Scholar Yet another justification for waiting to diagnose depression in equivocal cases is the tendency of generalists—when they inquire about depressive symptoms at all—not only to underdiagnose actual depression but also to diagnose depression when it is not actually there. A meta-analysis that pooled more than 50,000 cases found that generalists achieved a positive predictive value of 42% and a negative predictive value of 86%. Given the relative rarity of the depressed vs nondepressed condition, what this means is that in a sample of 100 patients, 10 patients with depression will be correctly identified, 10 will be missed, and 15 patients who are not depressed will be falsely given the diagnosis.17Mitchell AJ Vaze A Rao S Clinical diagnosis of depression in primary care: a meta-analysis.Lancet. 2009; 374: 609-619Abstract Full Text Full Text PDF PubMed Scopus (777) Google Scholar It [medicine] always is directly hurtful; it may sometimes be indirectly beneficial.Oliver Wendell Holmes SrCurrents and Counter-Currents in Medical ScienceThe person who takes medicine must recover twice, once from the disease and once from the medicine.Attributed to William Osler, MD Both Holmes and Osler speak truths that apply to patients in whom ADs have been newly prescribed. Not only can patients with depression develop medication-induced adverse effects long before mood improvement can be expected, but they can also experience the treatment as being as noxious as the illness being treated. The proof of these statements' validity is that as many as 70% of primary care patients fail to adhere to either short- or long-term AD treatment, citing adverse effects as the main reason for discontinuing use of their medication.18Nurnberg HG Hensley PL Gelenberg AJ Fava M Lauriello J Paine S Treatment of antidepressant-associated sexual dysfunction with sildenafil: a randomized controlled trial.JAMA. 2003; 289: 56-64Crossref PubMed Scopus (200) Google Scholar Choosing among the many ADs currently on the US market (Table 2) presents a challenge to primary care physicians, who write more than 75% of the prescriptions for these drugs.22Hu XH Bull SA Hunkeler EM et al.Incidence and duration of side effects and those rated as bothersome with selective serotonin reuptake inhibitor treatment for depression: patient report versus physician estimate.J Clin Psychiatry. 2004; 65: 959-965Crossref PubMed Scopus (189) Google Scholar That choice is complicated by clinical trial data whose applicability to real-life practice is brought into question by unrepresentative patient populations, the fact that all available medications are predicated on an understanding of the underlying mechanism in depression that is outdated, and the impact of vigorous marketing claims that are not borne out by the research.TABLE 2Commonly Used AntidepressantsDose (mg/d)AntidepressantStartingTherapeuticMaximumSelected first-generation antidepressants Tricyclics Tertiary amine Amitriptyline2550-200300 Clomipramine (Anafranil)2550-200300 Doxepin (Sinequan)2550-200300 Imipramine (Tofranil)2550-200300 Secondary amine Desipramine (Norpramin)2550-200300Nortriptyline (Pamelor)2550-150150Selected second-generation antidepressants SSRIs Citalopram (Celexa)1010-6080 Escitalopram (Lexapro)1010-2040 Fluoxetine (Prozac)1020-6080 Paroxetine (Paxil)1020-5060 Sertraline (Zoloft)2525-200200 SNRIs Desvenlafaxine (Pristiq)5050-100100 Duloxetine (Cymbalta)3030-90120 Venlafaxine (Effexor XR)37.537.5-375 Serotonin antagonist Mirtazapine (Remeron)7.515-4545 Norepinephrine and dopamine reuptake inhibitors Bupropion SR (Wellbutrin)100100-400400 Bupropion XL (Wellbutrin)150150-450450SNRI = serotonin and norepinephrine reuptake inhibitor; SR = sustained release; SSRI = selective serotonin reuptake inhibitor; XL = extended release. All doses are for oral preparation taken once daily except for bupropion SR, which is taken twice daily, and venlafaxine (Effexor SR), which can be taken once a day or in divided doses.6Gelenberg AJ Hopkins HS Assessing and treating depression in primary care medicine.Am J Med. 2007; 120: 105-108Abstract Full Text Full Text PDF PubMed Scopus (31) Google Scholar, 10Whooley MA Avins AL Miranda J Browner WS Case-finding instruments for depression: two questions are as good as many.J Gen Intern Med. 1997; 12: 439-445Crossref PubMed Scopus (1357) Google Scholar 19Zimmerman M Posternak MA Attiullah N et al.Why isn't bupropion the most frequently prescribed antidepressant?.J Clin Psychiatry. 2005; 66: 603-610Crossref PubMed Scopus (42) Google Scholar, 20Mann JJ The medical management of depression.N Engl J Med. 2005; 353: 1819-1834Crossref PubMed Scopus (338) Google Scholar, 21Adams SM Miller KE Zylstra RG Pharmacologic management of adult depression.Am Fam Physician. 2008; 77: 785-792PubMed Google Scholar Open table in a new tab SNRI = serotonin and norepinephrine reuptake inhibitor; SR = sustained release; SSRI = selective serotonin reuptake inhibitor; XL = extended release. All doses are for oral preparation taken once daily except for bupropion SR, which is taken twice daily, and venlafaxine (Effexor SR), which can be taken once a day or in divided doses.6Gelenberg AJ Hopkins HS Assessing and treating depression in primary care medicine.Am J Med. 2007; 120: 105-108Abstract Full Text Full Text PDF PubMed Scopus (31) Google Scholar, 10Whooley MA Avins AL Miranda J Browner WS Case-finding instruments for depression: two questions are as good as many.J Gen Intern Med. 1997; 12: 439-445Crossref PubMed Scopus (1357) Google Scholar 19Zimmerman M Posternak MA Attiullah N et al.Why isn't bupropion the most frequently prescribed antidepressant?.J Clin Psychiatry. 2005; 66: 603-610Crossref PubMed Scopus (42) Google Scholar, 20Mann JJ The medical management of depression.N Engl J Med. 2005; 353: 1819-1834Crossref PubMed Scopus (338) Google Scholar, 21Adams SM Miller KE Zylstra RG Pharmacologic management of adult depression.Am Fam Physician. 2008; 77: 785-792PubMed Google Scholar Pharmaceutical studies that guide physicians' treatment decisions are frequently based on individuals not typical of patients in most practices. Zimmerman et al23Zimmerman M Mattia JI Posternak MA Are subjects in pharmacological treatment trials of depression representative of patients in routine clinical practice?.Am J Psychiatry. 2002; 159: 469-473Crossref PubMed Scopus (357) Google Scholar wanted to know what proportion of depressed patients in their Rhode Island outpatient psychiatric practice would be eligible for such studies. They distilled inclusion and exclusion criteria from 31 studies that appeared in 5 major psychiatric journals in the mid-1990s. Ruled ineligible were patients with bipolar depression, recent substance abuse, suicidal ideation, and comorbid Axis I disorders, including anxiety, borderline personality disorder, and depression that had lasted either too long or not long enough. Only 41 (12%) of 346 patients would have made the cut. Prescribers should assume that criterion standard randomized controlled trials are at best general guides for how to medicate actual patients, most of whom will have 1 or more inconvenient comorbid conditions rendering them ineligible for most research trials. Antidepressant treatment strategies are based nearly exclusively on the half-century-old monoamine hypothesis, which posits that depressive symptoms are driven by noradrenergic, serotonergic, and dopaminergic system abnormalities that will be corrected with drugs that raise brain monoamine levels.24Rapaport MH Future drugs for the treatment of depression: the need to look beyond monoamine systems.CNS Spectr. 2009; 14: 14-16PubMed Google Scholar All ADs in current use are thought to work through monoaminergic manipulation, even as the mechanisms by which this occurs remain incompletely defined.25aan het Rot M Mathew SJ Charney DS Neurobiological mechanisms in major depressive disorder.CMAJ. 2009; 180: 305-313PubMed Google Scholar Depression is increasingly understood to derive not only from perturbations in monoamine circuits—a so-called chemical imbalance in the brain—but also from "the cumulative impact of genetics, adverse events in childhood and ongoing or recent stress" that affect brain-derived neurotrophic factor levels, hypothalamic-pituitary-adrenal axis function, and glutamate-mediated toxicity in multiple brain regions.25aan het Rot M Mathew SJ Charney DS Neurobiological mechanisms in major depressive disorder.CMAJ. 2009; 180: 305-313PubMed Google Scholar With only half of depressed patients responding to monoaminergic ADs, Rapaport24Rapaport MH Future drugs for the treatment of depression: the need to look beyond monoamine systems.CNS Spectr. 2009; 14: 14-16PubMed Google Scholar cites evidence for multiple pathophysiologic processes that may contribute to what he calls the complex heterogeneous syndrome of depression that may not respond to available ADs. "Our most recent consensus suggests that the depressive disorders reflect the interplay between these biological systems and psychosocial experiences, such as early-life trauma and current life stressors," Rapaport writes.24Rapaport MH Future drugs for the treatment of depression: the need to look beyond monoamine systems.CNS Spectr. 2009; 14: 14-16PubMed Google Scholar Although all AD classes demonstrate comparable efficacy in treating depression,26Maurer D Colt R An evidence-based approach to the management of depression.Prim Care. 2006; 33 (vii.): 923-941Abstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar, 27Richelson E Pharmacology of antidepressants.Mayo Clin Proc. 2001; 76: 511-527Abstract Full Text Full Text PDF PubMed Scopus (190) Google Scholar, 28Williams Jr, JW Mulrow CD Chiquette E Noel PH Aguilar C Cornell J A systematic review of newer pharmacotherapies for depression in adults: evidence report summary.Ann Intern Med. 2000; 132: 743-756Crossref PubMed Scopus (352) Google Scholar second-generation ADs have become first-line treatment as a result of vigorous marketing claims that they promote better adherence and are safer in overdose than the cardiotoxic first-generation tricyclic antidepressants (TCAs).29Gartlehner G Gaynes BN Hansen RA et al.Comparative benefits and harms of second-generation antidepressants: background paper for the American College of Physicians.Ann Intern Med. 2008; 149: 734-750Crossref PubMed Scopus (186) Google Scholar Although patients have reported tolerating second-generation ADs—so-called modern or atypical ADs—better than first-generation drugs,30Mulrow CD Williams Jr, JW Chiquette E et al.Efficacy of newer medications for treating depression in primary care patients.Am J Med. 2000; 108: 54-64Abstract Full Text Full Text PDF PubMed Scopus (116) Google Scholar assertions of improved tolerance belie patient actions. An 84-study meta-analysis by Trindade et al31Trindade E Menon D Topfer LA Coloma C Adverse effects associated with selective serotonin reuptake inhibitors and tricyclic antidepressants: a meta-analysis.CMAJ. 1998; 159: 1245-1252PubMed Google Scholar showed no difference in dropout rates between those taking TCAs and selective serotonin reuptake inhibitors (SSRIs), although the same study found distinct differences between the 2 drug classes in terms of adverse effects that patients considered unacceptable. Although the 2 classes did not differ in the prevalence of headache, tremor, urinary disturbance, or hypotension, TCAs were substantially more likely to induce such anticholinergic symptoms as dry mouth, constipation, dizziness, sweating, and blurred vision, and SSRIs were associated with substantially more nausea, anorexia, diarrhea, insomnia, nervousness, agitation, and anxiety.31Trindade E Menon D Topfer LA Coloma C Adverse effects associated with selective serotonin reuptake inhibitors and tricyclic antidepressants: a meta-analysis.CMAJ. 1998; 159: 1245-1252PubMed Google Scholar Knowing that all ADs have similar efficacy, the generalist faced with choosing an appropriate AD would do well to base rational treatment decisions on differences in side effects among the available ADs (for prescribing principles, see Table 3). Aggressive side-effect management can improve adherence, enhance comfort and function, and obviate premature discontinuation.40Kelly K Posternak M Alpert JE Toward achieving optimal response: understanding and managing antidepressant side effects.Dialogues Clin Neurosci. 2008; 10: 409-418PubMed Google Scholar Side effects can even be harnessed for their therapeutic value, as this review illustrates.TABLE 3Prescribing Principles for Antidepressant Therapy 1.Do not rush to prescribe ADs for mild depressions, adjustment disorders, or depressive syndromes that do not meet full criteria for major depression; watchful waiting, combined with supportive visits with the physician, may cause the symptoms to remit14Ackermann RT Williams Jr, JW Rational treatment choices for non-major depressions in primary care: an evidence-based review.J Gen Intern Med. 2002; 17: 293-301Crossref PubMed Scopus (65) Google Scholar2.Inform patients of potential side effects and how they will be managed (early ones will be transient and bearable; late-developing or persistent effects may necessitate dosage adjustment or other antidote)3.Warn patients that adverse effects will likely occur before substantial benefit, which may not arrive for several weeks26Maurer D Colt R An evidence-based approach to the management of depression.Prim Care. 2006; 33 (vii.): 923-941Abstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar, 31Trindade E Menon D Topfer LA Coloma C Adverse effects associated with se
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