Zoloft Controlled Substance Status: Safety, Classification, & Misuse Risks

Naomi Carr
Dr. David Miles
Written by Naomi Carr on 02 May 2025
Medically reviewed by Dr. David Miles on 02 May 2025

Zoloft is an antidepressant medication containing sertraline, which is not classified as a controlled substance. This means that it is unlikely to cause abuse, misuse, or addiction and can be safely used to treat a range of mental health conditions.

Key takeaways:
  • Zoloft (sertraline) is a selective serotonin reuptake inhibitor (SSRI), which is a class of antidepressant medications.
  • Zoloft is not a controlled substance.
  • Zoloft can be safely used as a long-term treatment if it is taken as prescribed.
a photo of a Zoloft pill box with the words

Is Zoloft a controlled substance?

Zoloft is not a controlled substance as it has recognized medical uses and little risk of abuse, addiction, or harm. Controlled substances are regulated as they have the potential for abuse and addiction, which may result in limited refills or treatment only being prescribed for the short term.

Zoloft (sertraline) is a selective serotonin reuptake inhibitor (SSRI), which is a class of antidepressants. It is approved to treat major depressive disorder (MDD), obsessive-compulsive disorder (OCD), post-traumatic stress disorder (PTSD), panic disorder (PD), social anxiety disorder (SAD), and premenstrual dysphoric disorder (PMDD).

Antidepressants include SSRIs, serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), monoamine oxidase inhibitors (MAOIs), and atypical antidepressants. None of these classes of antidepressant medications contain controlled substances, as these medications do not carry a risk of addiction or misuse potential.

Esketamine, a nasal spray that is approved to treat depression, is a Schedule III controlled substance. It must be administered in a certified facility by a healthcare provider and cannot be taken home for self-administration, as there is potential for misuse and abuse.

Risk for misuse and addiction

Zoloft is unlikely to be misused or to cause the development of addiction. Although Zoloft impacts mood, it does not create a sense of euphoria or ‘high’ that is commonly seen with addictive substances. Because of this, people taking Zoloft are unlikely to experience cravings that typically precede the behaviors and consequences of physical and psychological addiction.

Can Zoloft be misused?

Zoloft is unlikely to be misused, as it does not create a ‘high’ and, therefore, is not considered a drug of abuse. However, Zoloft might be misused by taking higher or more frequent doses than prescribed or alongside other substances. For example, there are reports of Zoloft and other SSRIs being used alongside MDMA to enhance its euphoric effects and reduce its adverse effects.

Additionally, there may be a risk of misuse in people ending Zoloft treatment. The occurrence of severe discontinuation symptoms might cause Zoloft misuse in an attempt to reduce unpleasant effects. However, when Zoloft treatment is stopped, it is common for the prescribing doctor to advise about safe tapering and monitor the individual.

Can you develop a dependence on Zoloft?

That being said, prolonged Zoloft use can result in the development of physical dependence. Over time, the brain adapts to the effects of the medication and requires its continued use for normal functioning. Zoloft increases the level of serotonin in the brain, which means that if the medication is stopped, the brain experiences a sudden drop in serotonin.

This can cause discontinuation syndrome, which is a set of physical and psychological symptoms caused by the stoppage or reduction of Zoloft. Symptoms of discontinuation syndrome (sometimes referred to as withdrawal symptoms) can include:

  • Tiredness
  • Headaches
  • Sweating
  • Aches and pains
  • Insomnia
  • Vivid dreams
  • Nausea and vomiting
  • Dizziness
  • Irritability
  • Agitation
  • Low mood
  • Suicidal ideation
  • Mania
  • Sensory disturbances, including ‘brain zaps’ which feel like electric-shock sensations

These symptoms can range from mild to severe and are likely to be worse if the medication is stopped abruptly after prolonged use. Typically, symptoms will emerge within the first few days of stopping the medication and can last several weeks.

Dependence vs. Addiction

Although withdrawal symptoms can be a sign of addiction, Zoloft dependence and discontinuation syndrome differ from addiction. Physical dependence can cause discontinuation syndrome, while addiction causes harmful behaviors and consequences, including:

  • Cravings and drug-seeking behaviors
  • Increasing the dosage or frequency of use
  • Impairments in social, professional, or personal functioning due to use

Prescription and safe use guidelines

Zoloft can only be obtained through a prescription. Because Zoloft is not a controlled substance, there are no restrictions on prescription refills. It can be used as a long-term treatment to manage depression or other mental health conditions.

Typically, the prescribing doctor will conduct regular reviews to monitor the efficacy of Zoloft treatment and manage any issues with treatment. Zoloft should be taken exactly as prescribed to help prevent adverse effects. New treatment will be gradually increased to find the therapeutic dose, while discontinuing treatments will be gradually reduced to help prevent discontinuation syndrome.

For safe use, never take more or less Zoloft than is prescribed or stop taking the medication suddenly or without professional advice. Also, never give your prescription to someone else, even if they have similar symptoms.

FAQs

Common questions about Zoloft controlled status

Is it safe to stop taking Zoloft abruptly?

People taking Zoloft should not stop abruptly, as this can increase the risk and severity of discontinuation syndrome symptoms. Zoloft doses should be gradually reduced.

How does Zoloft compare to benzodiazepines?

Zoloft is an antidepressant medication that can treat depression, anxiety disorders, post-traumatic stress disorder (PTSD), obsessive-compulsive disorder (OCD), and premenstrual dysphoric disorder (PMDD). Benzodiazepines are usually used to treat anxiety disorders or insomnia.

Zoloft is not a controlled substance and can be used as a long-term treatment with few adverse effects. Benzodiazepines are Schedule IV controlled substances and should only be used short-term, as they have a risk of addiction and abuse.

Is Zoloft the same as Xanax?

No, Zoloft is sertraline, an SSRI antidepressant, while Xanax is alprazolam, a benzodiazepine, which is a tranquilizer or sedative. Both Zoloft and Xanax can help reduce symptoms of anxiety, although they are different medications with different actions. Xanax is a Schedule IV controlled substance, and Zoloft is not a controlled substance.

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Resources:

  1. Roerig, Pfizer, Inc. (Revised 2016). Zoloft (Sertraline Hydrochloride) Label. FDA. Retrieved from
  2. Preuss, C.V., Kalava, A., & King, K.C. (Updated 2023). Prescription of Controlled Substances: Benefits and Risks. In: StatPearls [Internet]. Treasure Island, FL: StatPearls Publishing. Retrieved from
  3. Sheffler, Z.M., Patel, P., & Abdijadid, S. (Updated 2023). Antidepressants. In: StatPearls [Internet]. Treasure Island, FL: StatPearls Publishing. Retrieved from
  4. Johnson & Johnson. (2025). Spravato (Esketamine). Spravato. Retrieved from
  5. Chiappini, S., Vickers-Smith, R., Guirguis, A., Corkery, J.M., Martinotti, G., & Schifano, F. (2022). A Focus on Abuse/Misuse and Withdrawal Issues with Selective Serotonin Reuptake Inhibitors (SSRIs): Analysis of Both the European EMA and the US FAERS Pharmacovigilance Databases. Pharmaceuticals (Basel, Switzerland), 15(5), 565. Retrieved from
  6. Gabriel, M., & Sharma, V. (2017). Antidepressant Discontinuation Syndrome. CMAJ: Canadian Medical Association Journal, 189(21), E747. Retrieved from
  7. Bounds, C.G., & Patel, P. (Updated 2024). Benzodiazepines. In: StatPearls [Internet]. Treasure Island, FL: StatPearls Publishing. Retrieved from
  8. Pharmacia & Upjohn Co, Pfizer, Inc. (Revised 2016). Xanax Label. FDA. Retrieved from

Activity History - Last updated: 02 May 2025, Published date:


Reviewer

David is a seasoned Pharmacist, natural medicines expert, medical reviewer, and pastor. Earning his Doctorate from the Medical University of South Carolina, David received clinical training at several major hospital systems and has worked for various pharmacy chains over the years. His focus and passion has always been taking care of his patients by getting accurate information and thorough education to those who need it most. His motto: "Good Information = Good Outcomes".

Activity History - Medically Reviewed on 01 May 2025 and last checked on 02 May 2025

Medically reviewed by
Dr. David Miles

Dr. David Miles

PharmD

Reviewer

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