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While antidepressants may be the drug of choice for depression, they also have FDA approval as treatments for other medical disorders. For example, antidepressants help treat obsessive-compulsive disorder, social phobia, panic disorder, generalized anxiety disorder (GAD), and post-traumatic stress disorder (PTSD). Antidepressants also have non-FDA-approved, off-label indications. This activity reviews the indications, contraindications, action, adverse events, and other key elements of antidepressant therapy in the clinical setting as it relates to the essential points needed by members of an interprofessional team managing the care of patients receiving antidepressant medications for conditions that respond to this medication class. Objectives: Identify the approved and off-label indications for antidepressant medications. Summarize the mechanism of action of the various class members in the antidepressant drug class. Outline the adverse events of various antidepressant medications. Explain the importance of antidepressant therapy and how it affects therapeutic strategy as a component of care coordination and communication among the interprofessional team when using these agents to achieve therapeutic outcomes. Access free multiple choice questions on this topic.

The toxicity of antidepressants varies greatly not only between classes but within them as well. Antidepressants are frequently used to self-poison in an attempt to commit suicide, particularly in women. Older tricyclic antidepressants (TCAs) are more toxic than newer antidepressant classes. Such as selective serotonin reuptake inhibitors (SSRIs). Researchers can track drug toxicity using the fatal toxicity index, a ratio of self-poisoning mortality rates to prescription rates. Researchers may also employ a case fatality index, which compares fatal versus non-fatal self-poisoning attempts. With that said, clinicians may wish to alter treatment strategies depending on a patient’s suicide risk.[43] According to the literature review, toxicity is higher for TCAs and MAO inhibitors followed by venlafaxine, bupropion, and mirtazapine and is lower for SSRIs. Among the selective serotonin reuptake inhibitors, citalopram and fluvoxamine appear to be associated with higher case fatality rates in overdose.[44] SSRI Poisoning Clinical Features CNS- drowsiness, tremor CVS- QRS and QTc interval prolongation(especially with citalopram and escitalopram) Potential serotonin syndrome: hyperthermia, hypertonia, hyperreflexia, clonus. Management Secure airway, breathing, and circulation; intubate as clinically indicated. Treat prolonged QRS intervals with sodium bicarbonate Prolonged QTc leading to torsades- Administer magnesium sulfate 2 g IV. Treat seizures with benzodiazepines (e.g., lorazepam 1 to 2 mg IV) as needed. SSRIs are relatively safe, although serotonin syndrome is common in overdose. The exception is citalopram, which is significantly associated with QTc prolongation.[45] SNRI Poisoning Clinical Features Tachycardia Hypertension Electrocardiogram changes (e.g., prolongation of QT interval, bundle branch block, QRS prolongation), ventricular tachycardia Changes in the level of consciousness (ranging from somnolence to coma) Mydriasis Serotonin syndrome Rhabdomyolysis Liver necrosis Death Management In case of acute overdose with SNRI, the clinician should ensure an adequate airway, breathing, and circulation. For serotonin syndrome, specific treatment (such as with cyproheptadine may be considered) Treat prolonged QRS intervals with sodium bicarbonate Prolonged QTc leading to torsades- Administer magnesium sulfate 2 g IV. Consider extracorporeal life support in severe poisoning with venlafaxine.[46] Atypical Antidepressants Poisoning Bupropion

For serotonin syndrome, specific treatment (such as with cyproheptadine may be considered) Treat prolonged QRS intervals with sodium bicarbonate Prolonged QTc leading to torsades- Administer magnesium sulfate 2 g IV. Consider extracorporeal life support in severe poisoning with venlafaxine.[46] Atypical Antidepressants Poisoning Bupropion Clinical features Tachycardia Hypertension Seizures[47] Management Ensure an adequate airway, oxygenation, and ventilation. EEG monitoring is recommended for the first 48 hours post-ingestion. Administer intravenous benzodiazepine for seizures.[48][49] Mirtazapine Clinical Features Disorientation Drowsiness Impaired memory Bradyarrhythmias[50] Management Ensure an adequate airway, oxygenation, and ventilation Monitor cardiac rhythm and vital signs. Treat arrhythmias according to ACLS and PALS protocol. Serotonin Modulators Poisoning Trazodone Clinical Features Arrhythmias Respiratory arrest Coma Priapism[51] Management Treatment should be symptomatic and supportive in the case of hypotension or excessive sedation. Priapism requires urgent evaluation by a urologist. In patients with ischemic priapism, intracavernosal injection such as phenylephrine.[52] Vilazodone Clinical Features drowsiness vomiting tachycardia serotonin syndrome(altered mental status, autonomic instability, and neuromuscular abnormalities)[53] Management Ensure an adequate airway, breathing, and circulation. Serotonin syndrome-  Vilazodone has up to 30-fold higher potency for serotonin reuptake inhibition than conventional SSRIs. Consequently, management of serotonin syndrome is the mainstay of therapy. Treatment of serotonin syndrome. Administer benzodiazepines (e.g., lorazepam 1 to 2 mg IV per dose) till the patient is asymptomatic. Administer IV fluids. Consider sedation, paralysis, and endotracheal intubation for severe hyperthermia. Administer antidote cyproheptadine(antagonist at 5-HT1A and 5-HT2A receptors).[54] TCAs Poisoning Clinical Features Anticholinergic- Dilated pupils, absent bowel sounds, constipation, urinary retention Cardiac- Tachycardia, hypotension, conduction abnormalities, QRS duration >100 msec Neurologic- Sedation, seizures Management Maintain airway, breathing, circulation Treat hypotension with intravenous crystalloid. Administer vasopressors such as norepinephrine in refractory hypotension. If QRS >100 msec, administer IV sodium bicarbonate.

Cardiac- Tachycardia, hypotension, conduction abnormalities, QRS duration >100 msec Neurologic- Sedation, seizures Management Maintain airway, breathing, circulation Treat hypotension with intravenous crystalloid. Administer vasopressors such as norepinephrine in refractory hypotension. If QRS >100 msec, administer IV sodium bicarbonate. Administer activated charcoal(1g/kg) if the patient presents within 2 hours of ingestion; often, charcoal is avoided due to the presence of ileus. Administer benzodiazepines (lorazepam 2 mg IV) for seizures. QRS interval longer than 100 ms is a reliable predictor of serious complications.[55] MAOI Poisoning Clinical Features Serotonin syndrome Hypertensive crisis Management Establish adequate airway, breathing, and circulation. Administer parenteral agents for hypertensive crisis. Serotonin syndrome- Administer IV fluids, benzodiazepines, and cyproheptadine.[56] NMDA antagonist (esketamine) Poisoning Clinical Features Sedation Dissociation Ulcerative or Interstitial Cystitis Embryo-fetal Toxicity Management Establish adequate airway, breathing, and circulation. There is no specific antidote for esketamine overdose. In the case of overdose, clinicians should consider the possibility of multiple drug involvement. Contact a certified poison control center for the most up-to-date information on managing overdosage. Dextromethorphan/bupropion poisoning Clinical Features Seizures Serotonin Syndrome Psychosis[57] Management Ensure an adequate airway, oxygenation, and ventilation. There is no specific antidote. Provide supportive care. Administer benzodiazepines for seizures.[49] Consult a medical toxicologist or a certified poison control center.[58]

While antidepressants are beneficial in treating depression and its other indications, many patients fail to receive adequate treatment. To effectively manage depression, a clinician must employ an interprofessional team-centered approach to effectively detect and diagnose the depression, provide patient education, use evidence-based pharmacotherapy, provide close-follow up for compliance, identify side effects, and determine treatment effectiveness.[59] Studies show multiple factors contribute to patient compliance with antidepressant medications. Generally, concerns about drug side effects were predictive of adherence.[60] Patient comorbidities can also contribute to compliance with antidepressant medications. Particularly, conditions that impact one’s cognitive status can lead to non-compliance.[61] Alcohol or substance abuse, cardiovascular disease, metabolic disorders, young age, low-income residents, and old-generation antidepressant medication usage were predictive of lower adherence, particularly in the acute phase.[62] Identifying and addressing these concerns is pivotal in the management of depression and the prescription of antidepressant medications. Several randomized controlled trials support the collaborative care approach in treating depression. Suggestions are that the program includes a depression care manager, psychiatric consultant, prescribing physician, and the patient. The depression care manager will manage the antidepressants, provide education, and coordinate referrals if necessary. The psychiatric consultant will be responsible for improving treatment strategies in patients who are not meeting expectations.[63] Patients may be receiving more than one antidepressant medication at a time. Hence it is essential to identify all the drugs involved in poisoning for the emergency physicians and triage nurses. Other healthcare team members who must contribute to antidepressant care include the pharmacist and the nursing staff. Psychiatric specialty nurses are best equipped to recognize treatment failure, counsel patients on the medication, monitor adverse events, and assess compliance. Pharmacists can verify agent selection and dosing and perform medication reconciliation for drug interactions. Both pharmacists and nurses need open access to the prescriber in case of concern.

Other healthcare team members who must contribute to antidepressant care include the pharmacist and the nursing staff. Psychiatric specialty nurses are best equipped to recognize treatment failure, counsel patients on the medication, monitor adverse events, and assess compliance. Pharmacists can verify agent selection and dosing and perform medication reconciliation for drug interactions. Both pharmacists and nurses need open access to the prescriber in case of concern. In overdose of antidepressants, emergency department physicians should rapidly stabilize the patient ensuring adequate airway, breathing, and circulation. Cardiac arrhythmias, serotonin syndrome, and seizures require ICU care under the supervision of a critical care physician. Medical toxicologists should be consulted for severe poisoning. Deliberate overdose requires consultation with a psychiatrist. As illustrated above, clinicians (MDs, DOs, NPs, PAs), specialists, pharmacists, nurses, and other healthcare providers are involved in taking care of the patient receiving antidepressant therapy. All interprofessional team members functioning as one unit can maximize efficacy and minimize adverse reactions, translating to optimal patient outcomes. [Level 5]