Sertraline (Zoloft) is an antidepressant belonging to the group selective serotonin reuptake inhibitors (SSRIs). It is now one of the most widely prescribed antidepressants and antianxiety medications. Sertraline has been available in the United States since 1992 and by the late 1990s, it became one of the most popular medications ever prescribed: by the time the US patent expired in 2006, it was estimated to have grossed over $3 billion in sales.
A 2009 pooled analysis compared 12 new-generation agents (SSRIs and other newer antidepressants), factoring in efficacy, acceptability, and cost, and concluded that sertraline had the best balance of all of these factors.
Uses of Sertraline
- Major depressive disorder: Sertraline can be begun at 25–50 mg/day, and increased in 25–50 mg increments to a target dose of 100–150 mg/day. It can also be used for the maintenance treatment of depression.
- Anxiety disorders: Sertraline (Zoloft) is the first-line agent for pharmacological treatment of anxiety disorders. The anxiolytic effects of sertraline are not immediate but take days or weeks to develop after commencing drug therapy, suggesting that adaptive responses to the initial effects of these drugs that develop over time are important. The usual starting dose of sertraline for adults with anxiety disorders is 12.5 mg/day, with target dose of 50 mg/day, reaching up to a maximum of 200 mg/day. Sertraline may be particularly effective treatment for anxiety in the elderly based on its low propensity for drug interactions and short half-life.
- Social anxiety disorder: An initial dose of 50 mg/day of sertraline is needed. After 4 weeks, the dose could be increased by 50 mg/day every 3 weeks up to a maximum of 200 mg/day. In the event of intolerable side effects, doses could be reduced to a minimum of 50 mg/day. Sertraline has been shown to be effective in treating social anxiety disorder in children and adolescents, especially when combined with cognitive-behavioral therapy.
- Generalized anxiety disorder (GAD): Sertraline administration leads to a statistically significant reduction in anxiety symptoms of GAD. Sertraline 25–50 mg/day is efficacious in children and adolescents. In adults, 50–150 mg/day is needed.
- Obsessive-compulsive disorder (OCD): Sertraline is FDA-approved for the treatment of OCD. It is a first-line pharmacotherapy for both acute and maintenance treatment of OCD in children and adults. Higher doses of sertraline are associated with better outcomes in OCD. Greater symptom improvement is seen in patients receiving 250–400 mg/day sertraline, with some patients responding to even higher doses. Discontinuing sertraline treatment is associated with an exacerbation of symptoms and worsening in quality of life.
- Panic disorder: There is currently evidence that sertraline is effective in the acute treatment of panic disorder. Patients are started on 25 mg/day for the first week and then the dose is escalated to 50 mg/day. Sertraline-treated patients experience significant reductions in panic attack frequency. Sertraline was also found to be efficacious in fixed-dose, with the 150 mg/day dose seeming to be the most effective dose. Maintenance treatment with sertraline is associated with continued improvement and protects patients from recurrence. It decreases the frequency of panic attacks by about 80 percent and decreases associated anticipatory anxiety. It results in an improvement of quality of life on most parameters. When stopping sertraline in patients with panic disorder, gradual discontinuation is recommended.
- Post-traumatic stress disorder (PTSD): Sertraline has been approved by the FDA for the treatment of PTSD in elders. Sertraline is the only medication that has been approved by the FDA to treat PTSD in children aged 12 to 18 years. The dose is 50–200 mg/day. It may be equally effective for the short-term treatment of PTSD symptoms. Sertraline shows a positive effect on the numbing and arousal symptoms of PTSD and on the comorbid symptoms of anxiety and depression. It is also effective in treating the major depressive disorders that are frequently seen among PTSD patients.
- Major depressive disorder in alcoholics: Sertraline has also been shown to reduce depressive symptoms among inpatient alcoholics, although the medication’s effects on preventing relapse to drinking have not been evaluated.
- Psychotic depression: Combination pharmacotherapy with olanzapine and sertraline is associated with higher remission rates in psychotic depression.
- Insomnia in psychiatric patients: In clinical practice, hypnotics often are prescribed concomitantly with antidepressants for patients with mood and anxiety disorders. Pharmacokinetic and pharmacodynamic studies of sertraline combined with zolpidem have been performed in healthy, nondepressed women, and no clinically significant interactions were identified.
- Postpartum depression (PPD): Sertraline has shown benefit in both preventing and treating PPD. Women at increased risk for PPD should consider initiating prophylactic sertraline in either late pregnancy or early postpartum.
- Autism spectrum disorders (ASD): Low-dose sertraline may be effective for anxiety associated with transitions and “insistence on sameness”.
- Premenstrual syndrome: Sertraline 50–150 mg/day is effective.
- Premature ejaculation: Treatment success is seen with sertraline 50 to 100 mg/day.
- Dementia: Antidepressants have been used to treat depressive symptoms, anxiety, and agitation in dementia. Sertraline has shown benefits in clinical trials. It has shown some efficacy for depressive symptoms and anxiety, and modest evidence of utility in agitation in some studies.
- Alzheimer’s disease and other neurocognitive disorders: Sertraline has efficacy in treating behavioral symptoms in patients with dementia and depression.
- Hallucinogen Persisting Perception Disorder (HPPD): Sertraline has been reported to help in selected cases.
- Traumatic brain injury: Depressive symptoms may respond to antidepressants: sertraline is not only effective in this regard but was also associated with cognitive improvement. When symptoms persist beyond a month, cognitive-behavioral therapy may be helpful. Alcohol should be forbidden until recovery is complete.
- Antisocial personality disorder: Sertraline has been associated with significant reductions in overt hostility, aggression, and antisocial behavior.
- Tourette and tic disorders: Sertraline starting dose is 12.5-25 mg/day, with a range of 25-200 mg/day, with maximum dose being 200-300 mg/day.
- Depression in cardiac patients: The Sertraline Antidepressant Heart Attack Randomized Trial (SADHART) tested the use of sertraline in 369 patients with acute myocardial infarctions or unstable angina. They found that the antidepressant improved depressive symptoms in patients with severe depression, with a better quality of life, and a trend toward fewer adverse cardiac events.
- Cancer-related fatigue: Sertraline is effective in improving fatigue among cancer patients with comorbid depressive symptoms.
- Premenopausal women with major depression were found to respond better to sertraline than imipramine, whereas postmenopausal women responded similarly to both agents.
- Perinatal depression and anxiety treatment: Treatment should be initiated at half of the recommended starting dose (25 mg/day) for 4 days, and doses should be increased by small increments (e.g., 25 mg per week) as tolerated until full remission is achieved. If the patient has a response to an initial trial of medication lasting 6 to 8 weeks, the same dose should be continued for a minimum of 6 months after full remission has been achieved to prevent a relapse. If there is no improvement after 6 weeks of drug therapy or if the patient has a response but then has a relapse, a medication change (within-class or different class) is recommended.
- Buspirone (Wellbutrin) coadministered with sertraline (Zoloft) was found to lead to improved abstinence rates at 26 weeks following smoking cessation.
- Paraphilic patients with sex addictions and comorbid depression showed a concurrent decrease in paraphilic behavior when their depressive symptoms improved with sertraline (Zoloft).
- The SSRI sertraline considerably reduced irritability and aggression in a small open-label trial with 11 personality disordered patients with impulsive aggression.
- There is also evidence that sertraline treatment reduces myocardial ischemia induced by mental stress.
Side Effects of Sertraline (Zoloft)
Side effects of sertraline or Zoloft are:
- Decreased appetite
- Dry mouth
- Male sexual dysfunction
- Gastrointestinal distress
- Suicidality: There is concern about the use of SSRIs in children and adolescents, due to reports of an increase in suicidal thoughts on starting treatment.
- ‘Serotonin reaction or syndrome’ (hyperthermia, muscle rigidity, cardiovascular collapse) can occur if given with MAOIs.
- Reports of an acute discontinuation syndrome, which can include general malaise, asthenia, dizziness, vertigo, headache, myalgia, loss of appetite, nausea, diarrhea, and abdominal cramps, warrant a very gradual reduction in dose if this medication is to be discontinued.
- Long-term adverse effects include weight gain with its associated risk for type 2 diabetes mellitus.
- Also, depressed patients must be monitored for suicidal thoughts and bipolar patients monitored for mania.
- It does not significantly increase the risk for most birth defects.
- Sertraline is least likely to lead to accumulation in the infant. The data suggest that sertraline is present in breast milk and in infant serum, albeit in low concentrations.
Supplied in the US as Oral solution: 20 mg/5 mL; and Tablets (mg): 25, 50, 100
Sertraline is well absorbed orally, and its blood level may be increased after the ingestion of food. It is advocated that the initial administration of sertraline should be after a meal.
Starting doses of sertraline should be low (25 mg/day) followed by gradual dosage increases, particularly in those above age 75. Therapeutic dosages will vary, ranging from 50 to 200 mg a day of sertraline.
Recommended dose range: 50-200 mg/day.
Initial dosing for major depressive disorder and OCD is typically at 50 mg per day, with escalation to 100 mg per day after 4 to 7 days of treatment.
Initial treatment of panic disorder, social anxiety disorder, and PTSD is more typically 25 mg per day.
Children in OCD studies were started at 25 mg per day, whereas adolescents in OCD studies were started at 50 mg per day.
Treatment of premenstrual dysphoric disorder is usually started at 50 mg per day given daily or during the 2 weeks of the luteal phase. Individual patients may demonstrate improved tolerability starting at lower doses. Not uncommonly, patients require an upward titration of the dose.
The dose range in most patients with anxiety or affective disorders is typically 100 to 200 mg a day, although some patients respond to 50 mg per day. Patients with OCD often require higher doses (50-200 mg/day) for full therapeutic effect.
If started at too high a dose, SSRIs may initially exacerbate symptoms of anxiety and, therefore, a lower starting dose (e.g., 25 to 50 mg of sertraline) is often indicated in elderly anxious individuals. Once it has been established that the patient is tolerating the starting dose, the dose should then be gradually increased to the usual therapeutic range
Sertraline inhibits the metabolism of other drugs, so the risk of interactions is there. Medications whose metabolism may be inhibited include cardiac antiarrhythmic drugs, antidepressants and antipsychotics, some benzodiazepine anxiolytics, steroids, some antihistamines and antibiotics, and antifungal agents.
It is also a potent inhibitor of P-glycoprotein that may elevate levels of protein-bound drugs, such as digoxin, digitoxin, calcium channel blockers, and some chemotherapy drugs.
Also, sertraline (Zoloft) may increase lamotrigine levels.
Sertraline was found, in premarketing trials, to possess a weak uricosuric effect, with a mean decrease of uric acid by 7 percent.
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