Unipolar major depressive disorder is a common, disabling, and costly disease that is the leading cause of ill health, early death, and suicide in the United States. care doctors, in particular family physicians, are the first responders in this silent epidemic.
Although more than a dozen different antidepressants in 7 distinct classes are widely used to treat depression in primary care, there is no evidence that one drug is superior to another. Comparative effectiveness studies have produced mixed results, and no specialty organization has published recommendations on how Activating and sedating antidepressants choose antidepressants in a rational, evidence-based manner. In this article we present the theory and evidence for an individualized, patient-centered treatment model for major depression designed around a targeted symptom cluster-based approach to antidepressant selection.
When using this model for healthy adults with major depressive disorder, the choice of antidepressants should
Activating and sedating antidepressants guided by the presence of 1 of 4 common symptom clusters: This model Activating and sedating antidepressants built to foster future research, provide a logical framework for teaching residents how to select antidepressants, and equip primary care doctors with a structured treatment strategy to deliver optimal patient-centered care in the management of a debilitating disease: Unipolar major depressive disorder is a common, debilitating chronic disease that affects 1 in 6 people in the United States during their lifetime.
Primary care doctors, especially family physicians, are the first responders in mental health care in the United States. Antidepressants are a heterogeneous family of medications that are pharmacologically divided into 7 "Activating and sedating antidepressants" classes Table 1: Comparative effectiveness meta-analyses designed to tease out differences in efficacy between antidepressants have produced mixed results.
So how should primary care doctors select which antidepressants to use? In the absence of clear evidence from comparative effectiveness studies, a reasonable way to begin answering this question is to examine how psychiatrists select antidepressants. A targeted, symptom cluster-based approach to choosing antidepressants reflects the belief of most psychiatrists that not all depression is the same 50 ; depression subtypes exist, and those differences may potentially be used to guide drug selection in a logical way.
Any primary care model for a symptom cluster-based approach to antidepressant selection must be centered on a set of occurring symptoms, each of which may effectively be treated by a pharmacologically appropriate class or classes of antidepressants.
Based on available evidence and expert consensus, the most common and clinically relevant symptoms accompanying depression are anxiety, fatigue, insomnia, and pain.
Each of these 4 symptoms is physiologically mediated by one or more monoamine neurotransmitter pathways. Activating and sedating antidepressants
Anxiety is the first symptom to consider in the current effort to build a rational treatment model for depression in primary care Table 2. As noted "Activating and sedating antidepressants," it is regulated by serotonergic neurons acting on the limbic system that controls fear. Two other SSRIs with important activating fluoxetine and sedating paroxetine action will be examined later in the context of other symptom clusters. Fatigue is the second symptom under consideration Table 3.
Energy, attention, concentration, and related cognitive functions are mediated by norepinephrine. Fluoxetine, an unusual SSRI with some norepinephrine reuptake inhibition, 34 is the most activating SSRI available and is preferred by most psychiatrists to treat depression with fatigue.
Two other SNRIs, duloxetine and milnacipran, with FDA indications to treat chronic pain, will be discussed later in the context of another symptom cluster. Insomnia is the third Activating and sedating antidepressants under consideration Table 4. As discussed earlier, insomnia is regulated by sleep centers in the brainstem, which involve 5HT 2A receptors.
Mirtazapine is a good choice for restoring body weight when weight loss is a concern. Under the current proposal, the best antidepressants for treating insomnia, hyperarousal, and weight loss are mirtazapine, paroxetine, trazodone, and
Activating and sedating antidepressants Table 4.
Pain is the last symptom to consider in the current effort to build a rational treatment model for depression Table 5. Pain is thought to be mediated by both serotonin and norepinephrine acting directly to potentiate the analgesic effects of the endogenous opioid system. Duloxetine is a SNRI that is FDA approved to treat major depression as well as painful diabetic peripheral neuropathy, fibromyalgia, and chronic musculoskeletal pain.
What has been used for decades as effective treatment for a number of chronic pain conditions—including idiopathic neuropathy, 58 fibromyalgia, 59 painful diabetic neuropathy, 60 prophylaxis of episodic migraine, 61 and chronic musculoskeletal pain 62 —are TCAs such as amitriptyline and nortriptyline. Although TCAs are older and in general less well-tolerated than newer antidepressants, they have a similar if not better efficacy in treating depression. An individualized, patient-centered treatment model for depression, created around a targeted symptom cluster-based approach to antidepressant selection, is described herein Tables 2 to 5.
In healthy adults with unipolar major depressive disorder, the choice of antidepressants should be guided primarily by the patient's dominant symptom cluster. Patients do not need to have all the symptoms in a symptom cluster "Activating and sedating antidepressants" warrant treatment. Further distinction between medications in the same cluster may be guided by comorbid medical or psychiatric conditions, previous response or lack thereof to a particular agent, preexisting renal or "Activating and sedating antidepressants" dysfunction, drug-drug interactions, frequency of dosing, and other factors.
Pregnancy raises special concerns, especially with regard to teratogenicity and safety during breastfeeding. Sertraline has the best safety record in pregnant patients, whereas paroxetine should be avoided if possible. Activating and sedating antidepressants has the best evidence in children and adolescents and is generally considered first-line treatment in this population.
This proposed symptom cluster-based treatment model is based on the highest-quality evidence available, plausible neurobiological mechanisms, and years of practical experience.
Activating and sedating antidepressants
Veteran primary care doctors may find these recommendations comparable to their current practices, which were developed through trial and error. Nevertheless, direct evidence to Activating and sedating antidepressants the use of a symptom cluster-based approach is very limited and complicated by studies with flawed designs and inadequate power.
Future research should also strive to elucidate the complete mechanism of action for antidepressants, which may lead to the discovery of new biological targets for rational drug design. Lastly, primary care doctors need to know what
Activating and sedating antidepressants do Activating and sedating antidepressants an initial antidepressant fails.
No strategy—whether by augmentation with a second antidepressant or switching antidepressants within or between classes—has been proven superior. Primary care doctors, particularly family physicians, are the first responders in this silent epidemic. While there are more than a dozen different antidepressants in 7 distinct classes that are widely used to treat depression in primary care, there is no evidence that one drug is superior to another.
In this article we presented the theory and evidence for an individualized, patient-centered treatment model for major depression that is designed around a targeted symptom cluster-based approach to antidepressant selection. Using this model in healthy adults with major depressive disorder, the choice of antidepressants should be guided by the presence of 1 of 4 common symptom clusters: This model was created to act as a practical construct to foster the design of future prospective, randomized trials that will put the symptom cluster-based approach to the test.
In addition, this model provides a logical framework for teaching residents how to choose antidepressants that goes beyond arbitrary Activating and sedating antidepressants and error.
Finally, the ultimate goal of the model is to equip primary care doctors with a structured treatment strategy to deliver optimal patient-centered care in the battle against depression.
LinMD and Michael B. In this window In a new window. Commonly Prescribed Antidepressants in Primary Care. Recommended Treatment for Depression with Anxiety. Recommended Treatment for Depression with Fatigue. Recommended Treatment for Depression with Insomnia. Recommended Treatment for Depression with Pain. Previous Section Next Section. Arch Gen Psychiatry ; CrossRef Medline Google Scholar.
The epidemiology of major depressive disorder: JAMA ; Twelve-month use of mental health services in the United States: "Activating and sedating antidepressants" for Health Care Policy and Activating and sedating antidepressants. Depression Guideline Panel, Vol 2: Practice guideline for of patients with major depressive disorder. American Psychiatric Association Press ; Using second-generation antidepressants to treat depressive disorders: Ann Intern Med ; The economic burden of depression in the United States: J Clin Psychiatry ; Recognition and treatment of depression in a primary care setting.
Americans' attitudes toward mental health treatment seeking: Psychiatr Serv ; Prevalence and treatment of mental disorders, to N Engl J Med ; Health Aff Millwood ; "Activating and sedating antidepressants" MMarcus SC. National patterns in antidepressant medication treatment. National Ambulatory Medical Care Survey: National Center for Health Statistics ; Adv Data ; Citalopram versus other anti-depressive agents for depression.
Cochrane Database Syst Rev ;
Activating and sedating antidepressants Escitalopram versus other antidepressive agents for depression. Cochrane Database Syst Rev ; 2: Fluoxetine versus other types of pharmacotherapy for depression.
Cochrane Database Syst Rev ; 4: Fluvoxamine versus other anti-depressive agents for depression. Cochrane Database Syst Rev ; 3: Paroxetine versus placebo and other agents for depressive disorders: Sertraline versus other antidepressive agents for depression.
An integrated analysis of the efficacy of desvenlafaxine compared with placebo in patients with major depressive disorder.
CNS Spectr ; Duloxetine versus other anti-depressive agents for depression. Cochrane Database Syst Rev ; Newer class of antidepressants similar in effectiveness, but side effects differ. Avoid prescribing a highly activating SSRI, such Activating and sedating antidepressants fluoxetine, for patients for. “Some antidepressants are identified as activating, and some are sedating,” Combs explains. Finding the right match for you is key. A sedating.
Antidepressants with Broda Tricyclic Antidepressants. Amitriptyline Activation vs. Sedation. Fluvoxamine Citalopram. Fluoxetine. Paroxetine. Sertraline.