Can You Take Sertraline with Clonazepam?

Severity assessment

Moderate. The primary concern is additive central nervous system (CNS) depression, leading to increased sedation, dizziness, and impaired psychomotor function, which can be significant enough to affect daily activities and safety [1, 2, 3].

Mechanism (plain English)

Clonazepam is a benzodiazepine that works by enhancing the effects of gamma-aminobutyric acid (GABA), a natural calming chemical in the brain. This slows down brain activity, leading to reduced anxiety, muscle relaxation, and sedation [1]. Sertraline is a selective serotonin reuptake inhibitor (SSRI) that increases the levels of serotonin, a neurotransmitter, in the brain. While sertraline primarily affects serotonin, it can also contribute to CNS depression [2]. When taken together, the combined CNS depressant effects of both medications can be amplified, leading to increased drowsiness, dizziness, and impaired coordination. There is generally no significant pharmacokinetic interaction, meaning neither drug substantially alters the way the other is processed by the body [4, 5].

Evidence level

Guideline-supported. Both the British National Formulary (BNF) and Australian Consumer Medicine Information (CMI) for clonazepam explicitly warn about additive CNS depressant effects when used with other CNS depressants, including antidepressants like sertraline [1, 2, 3].

Top regulator advisories (cite verbatim or close paraphrase)

• TGA (Australia): The Consumer Medicine Information (CMI) for Paxam (clonazepam) states: "You should not take central nervous system depressants, such as sedatives, tranquillisers, and hypnotics, while taking PAXAM. These medicines have the potential to increase the effects of PAXAM resulting in severe effects including coma and death" [3]. No pair-specific public advisory found for sertraline and clonazepam, but the general warning for clonazepam applies.
• MHRA / NICE (UK): The British National Formulary (BNF) states for both sertraline and clonazepam that "Both Sertraline and [Clonazepam] have effects on the CNS and can cause sedation, which might affect the ability to perform skilled tasks... In some cases, use of two or more drugs that have effects on the CNS might also increase the risk of CNS depressant effects (which could range from sedation to unconsciousness, coma, respiratory depression, and/or cardiovascular depression)" [1, 2].
• FDA / CDC (US): The FDA label for Klonopin (clonazepam) warns about risks from concomitant use with other CNS depressants, specifically opioids, leading to profound sedation, respiratory depression, coma, and death. While not specific to sertraline, the general principle of additive CNS depression applies to other CNS depressants [6]. The FDA label for Zoloft (sertraline) warns about serotonin syndrome with other serotonergic agents, but does not specifically mention an interaction with clonazepam regarding CNS depression [7].
• EMA (Europe): No specific pair-specific advisory found.

Clinical risk factors that elevate the danger

• Higher doses of either medication: Increased doses of clonazepam or sertraline will heighten the risk of additive CNS depression [1, 2].
• Concomitant use of other CNS depressants: Alcohol, opioids, other benzodiazepines, sedatives, or antihistamines will further exacerbate CNS depression [3, 6].
• Elderly patients: Older adults are more sensitive to the CNS depressant effects of these medications and may experience increased sedation, dizziness, and a higher risk of falls [1, 2].
• Patients with respiratory compromise: Individuals with conditions like sleep apnea or chronic obstructive pulmonary disease (COPD) are at increased risk of respiratory depression [3].
• Patients with hepatic impairment: Liver dysfunction can reduce the metabolism of clonazepam, leading to higher drug levels and increased CNS depression [6].

What a patient should be told

• Risk of increased drowsiness and dizziness: You may feel more sleepy, dizzy, or have difficulty concentrating when taking clonazepam and sertraline together. This can affect your ability to drive or operate machinery safely. Be cautious until you know how these medications affect you.
• Do not stop suddenly: Never stop taking either medication abruptly without consulting your doctor. Suddenly stopping clonazepam can lead to severe withdrawal symptoms, including seizures. Your doctor will guide you on a gradual reduction if needed.
• Watch for warning signs: Be aware of signs of excessive sedation, confusion, slurred speech, extreme weakness, or difficulty breathing. If you experience any of these, seek medical attention immediately.
• Discuss alternatives: If you are concerned about these side effects, talk to your doctor or pharmacist about potential alternative treatments or dosage adjustments. Do not change your medication regimen on your own.
• Urgent care triggers: Seek immediate medical help if you experience severe difficulty breathing, unresponsiveness, or extreme confusion.

Top 3 sources (with full citation)

1. Sertraline. BNF. NICE. https://bnf.nice.org.uk/interactions/sertraline/
2. Clonazepam. BNF. NICE. https://bnf.nice.org.uk/interactions/clonazepam/
3. Paxam (clonazepam) Consumer Medicine Information. Medsinfo. https://medsinfo.com.au/consumer-information/document/Paxam_CMI

Notes for the reviewing pharmacist

The interaction between clonazepam and sertraline is primarily pharmacodynamic, leading to additive CNS depression. While pharmacokinetic studies generally show no significant interaction [4, 5], the clinical impact of combined CNS depressant effects is well-established and highlighted in regulatory guidelines [1, 2, 3]. It is crucial to counsel patients on the risks of impaired psychomotor function, especially concerning driving and operating machinery. Particular attention should be paid to elderly patients and those with pre-existing respiratory or hepatic conditions, as they are at higher risk for adverse outcomes. Gradual tapering of clonazepam is essential if discontinuation is considered, to prevent severe withdrawal symptoms. The absence of specific EMA advisories for this exact pair does not negate the general warnings regarding CNS depressants from other major regulators.

Source metadata JSON

{
  "pair": "clonazepam + sertraline",
  "severity": "Moderate",
  "evidence_level": "Guideline-supported",
  "source_urls": "https://bnf.nice.org.uk/interactions/sertraline/;https://bnf.nice.org.uk/interactions/clonazepam/;https://medsinfo.com.au/consumer-information/document/Paxam_CMI;https://www.drugs.com/drug-interactions/clonazepam-with-sertraline-703-0-2057-0.html;https://pubmed.ncbi.nlm.nih.gov/10653204/;https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/017533s061lbl.pdf;https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/019839s74s86s87_20990s35s44s45lbl.pdf"
}