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Adderall Vs. Zoloft: Drug Comparison

Compare common side effects, interactions, warnings, and more.

Medical Review byMike Bohl, MD, MBA, MPH, MS, ALMNov 4, 2024

Medication Name

Adderall XR

*image for illustrative purpose only

Zoloft

*image for illustrative purpose only

Summary

Prescription only

The information below is about Adderall XR®, an extended-release formulation of mixed salts of a single-entity amphetamine product. This information may not be accurate for the immediate-release formulation, Adderall®.

Adderall XR (amphetamine/dextroamphetamine extended-release) contains amphetamine, a Schedule II controlled substance. It is a stimulant medication used primarily to treat attention-deficit hyperactivity disorder (ADHD) by increasing levels of dopamine and norepinephrine in the brain, which helps improve focus, attention, and impulse control. Its FDA-approved indications include ADHD in both children and adults, and it may also be used to treat narcolepsy, though this is more common with immediate-release formulations. Adderall XR comes in capsule form and is designed for once-daily dosing. Common side effects include insomnia, decreased appetite, and increased heart rate, while serious warnings include a boxed warning for potential abuse, dependence, and cardiovascular risks, especially in individuals with underlying heart conditions or a history of substance abuse. It also interacts with certain other medications.

Prescription only

Zoloft® (sertraline) is a selective serotonin reuptake inhibitor (SSRI) used to treat mood disorders by increasing available serotonin levels in the brain, which helps improve mood and reduce symptoms of anxiety and depression. Its FDA-approved indications include the treatment of major depressive disorder (MDD), obsessive-compulsive disorder (OCD), panic disorder (PD), post-traumatic stress disorder (PTSD), social anxiety disorder (SAD), and premenstrual dysphoric disorder (PMDD). Off-label uses may include the treatment of eating disorders and generalized anxiety disorder (GAD). Zoloft is available in tablet and oral solution forms, typically taken once daily. Common side effects include nausea, dizziness, insomnia, and sexual dysfunction, and it carries a boxed warning for an increased risk of suicidal thoughts and behaviors in children, adolescents, and young adults, particularly during the initial treatment period.

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Drug Category

Central nervous system (CNS) stimulant

Selective serotonin reuptake inhibitor (SSRI)

Approved Uses

Adderall XR (mixed salts of a single-entity amphetamine product) is indicated:

  • For the treatment of attention deficit hyperactivity disorder (ADHD) in adults and pediatric patients 6 years and older.

Zoloft (sertraline hydrochloride) is indicated for the treatment of:

  • Major depressive disorder (MDD)

  • Obsessive-compulsive disorder (OCD)

  • Panic disorder (PD)

  • Posttraumatic stress disorder (PTSD)

  • Social anxiety disorder (SAD)

  • Premenstrual dysphoric disorder (PMDD)

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Dosage

  • Typically taken orally once daily

  • Comes in 5 mg, 10 mg, 15 mg, 20 mg, 25 mg, and 30 mg extended-release capsules

  • Typically taken orally once daily

  • Comes in 25 mg, 50 mg, and 100 mg tablets and 20 mg/mL oral solution

Known Common Side Effects

Pediatric patients ages 6 to 12: Most common adverse reactions (≥5% and with a higher incidence than on placebo) were:

  • Loss of appetite

  • Insomnia

  • Abdominal pain

  • Emotional lability

  • Vomiting

  • Nervousness

  • Nausea

  • Fever

Pediatric patients ages 13 to 17: Most common adverse reactions (≥5% and with a higher incidence than on placebo) were:

  • Loss of appetite

  • Insomnia

  • Abdominal pain

  • Weight loss

  • Nervousness

Adults: Most common adverse reactions ≥5% and with a higher incidence than on placebo were:

  • Dry mouth

  • Loss of appetite

  • Insomnia

  • Headache

  • Weight loss

  • Nausea

  • Anxiety

  • Agitation

  • Dizziness

  • Fast heart beat

  • Diarrhea

  • Weakness

  • Urinary tract infections

Most common adverse reactions (≥5% and twice placebo) in pooled placebo-controlled MDD, OCD, PD, PTSD, SAD and PMDD clinical trials were:

  • Nausea

  • Diarrhea/Loose stool

  • Tremor

  • Indigestion

  • Decreased appetite

  • Excessive sweating

  • Ejaculation failure

  • Decreased libido

Interactions & Contraindications

  • Known hypersensitivity or idiosyncrasy to amphetamine

  • During or within 14 days following the administration of monoamine oxidase inhibitors (MAOI)

  • Drug interactions: alkalinizing agents (GI antacids and urinary), acidifying agents (GI and urinary)

  • Concomitant use of monoamine oxidase inhibitors (MAOIs), or use within 14 days of stopping MAOIs

  • Concomitant use of pimozide

  • Known hypersensitivity to sertraline or excipients

  • Zoloft oral solution only: Concomitant use of disulfiram

  • Drug interactions: protein-bound drugs, CYP2D6 substrates

Warnings & Precautions

  • Risks to patients with serious cardiac disease

  • Increased blood pressure and heart rate

  • Psychiatric adverse reactions

  • Long-term suppression of growth in pediatric patients

  • Seizures

  • Peripheral vasculopathy, including Raynaud’s phenomenon

  • Serotonin syndrome: Increased risk when coadministered with serotonergic agents (e.g., SSRIs, SNRIs, triptans), but also during overdosage situations

  • Motor and verbal tics, and worsening of Tourette’s syndrome

  • Pregnancy: May cause fetal harm

  • Lactation: Breastfeeding not recommended

  • Serotonin syndrome

  • Increased risk of bleeding

  • Activation of mania/hypomania

  • Seizures

  • Angle closure glaucoma

  • QTc prolongation

  • Sexual dysfunction

  • Pregnancy: Third trimester use may increase risk for persistent pulmonary hypertension and withdrawal in the neonate

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Boxed Warning

WARNING: ABUSE, MISUSE, AND ADDICTION

Adderall XR has a high potential for abuse and misuse, which can lead to the development of a substance use disorder, including addiction. Misuse and abuse of CNS stimulants, including Adderall XR, can result in overdose and death:

  • Before prescribing Adderall XR, assess each patient’s risk for abuse, misuse, and addiction.

  • Educate patients and their families about these risks, proper storage of the drug, and proper disposal of any unused drug.

  • Throughout treatment, reassess each patient’s risk and frequently monitor for signs and symptoms of abuse, misuse, and addiction.

WARNING: SUICIDAL THOUGHTS AND BEHAVIORS

Antidepressants increased the risk of suicidal thoughts and behaviors in pediatric and young adult patients.

Closely monitor for clinical worsening and emergence of suicidal thoughts and behaviors.

References

*This information is from the label for brand name Adderall XR®. See the Full Prescribing Information for more complete information. Dextroamphetamine sulfate, dextroamphetamine saccharate, amphetamine sulfate, and amphetamine aspartate, the active ingredients in Adderall XR, may also be the active ingredients in other medications, and this information may not be accurate for all medications that include the active ingredients dextroamphetamine sulfate, dextroamphetamine saccharate, amphetamine sulfate, and amphetamine aspartate.

*This information is from the label for brand name Zoloft®. See the Full Prescribing Information for more complete information. Sertraline, the active ingredient in Zoloft, may also be the active ingredient in other medications, and this information may not be accurate for all medications that include the active ingredient sertraline.

The information provided here is NOT MEDICAL ADVICE and is for informational and educational purposes only. The drug comparison tool does not determine eligibility for medications or treatments provided via the Hims/Hers platform. Consultation with a healthcare provider is required to assess suitability for any medical treatment based on individual health and medical history. All product names and associated trademarks are the property of their respective owners.

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