Clonazepam

Clonazepam, also known by the brand name Klonopin, is a long-acting benzodiazepine. It is used to prevent and treat anxiety disorders, seizures, agitation linked to psychosis, and obsessive-compulsive disorder (OCD), and there is some evidence it may help with bipolar mania. The drug has several effects: it reduces anxiety, stops seizures, acts as a sedative and hypnotic, and relaxes skeletal muscles. It is usually taken by mouth, but can also be given intravenously. Effects start within an hour and last eight to twelve hours in adults.

Common side effects include sleepiness, weakness, poor coordination, trouble concentrating, and agitation. Clonazepam can also impair memory formation. With long-term use, people may develop tolerance, dependence, and life-threatening withdrawal symptoms if they stop suddenly. About one-third of people who take benzodiazepines for more than four weeks become dependent. The risk of suicide rises, especially in those already depressed. Use during pregnancy can harm the fetus. Clonazepam works by binding to GABAA receptors, boosting the effect of the brain's main inhibitory neurotransmitter, GABA.

Clonazepam was patented in 1960 and approved in the United States in 1975 by Roche. It is available as a generic. In 2023, it was the 62nd most prescribed medication in the U.S., with over 10 million prescriptions. It is also commonly used as a recreational drug in many parts of the world.

**Medical uses**

Clonazepam is prescribed for short-term management of epilepsy, anxiety, OCD, and panic disorder (with or without agoraphobia).

**Seizures**

Clonazepam is a first-line treatment for acute seizures, but it is not suitable for long-term seizure control because tolerance to its anticonvulsant effects develops. It has been found effective in treating epilepsy in children, with seizure suppression occurring at low blood levels. It is sometimes used for certain rare childhood epilepsies, but it does not work for infantile spasms. It is mainly prescribed for acute epilepsy management and is effective for non-convulsive status epilepticus, though benefits are often temporary, and phenytoin may be needed for lasting control. It is also approved for typical and atypical absence seizures, and for infantile myoclonic and akinetic seizures. Some people with treatment-resistant epilepsy may benefit from long-term use; clorazepate, another benzodiazepine, may be an alternative due to its slower onset of tolerance.

**Anxiety disorders**

Clonazepam is approved for panic disorder with or without agoraphobia. It has also been found effective for other anxiety disorders, such as social phobia, though this is an off-label use. Short-term controlled trials have shown its effectiveness for panic disorder, and some long-term trials suggest benefit for up to three years without developing tolerance.

**Muscle disorders**

Clonazepam is a third-line treatment option for restless legs syndrome, though its use is still investigational. It can help with bruxism in the short term and responds well to low doses for REM sleep behavior disorder. It is also used for acute and chronic akathisia caused by antipsychotics, and for spasticity related to amyotrophic lateral sclerosis (ALS).

**Other**

Benzodiazepines like clonazepam are sometimes used to treat mania or aggression from acute psychosis, either alone or with first-line drugs like lithium, haloperidol, or risperidone. Studies vary on whether current evidence supports its use for acute mania. It is unknown if taking benzodiazepines with antipsychotics is more effective than antipsychotics alone, or if benzodiazepines are better than antipsychotics for urgent sedation. Clonazepam is used for hyperekplexia and many forms of parasomnia and other sleep disorders. It is not effective for preventing migraines. It is also used topically for burning mouth syndrome, acting on the TRPM8 ion channel.

**Contraindications**

Clonazepam should not be used in cases of coma, current alcohol use disorder, current substance use disorder, or respiratory depression.

**Adverse effects**

In September 2020, the U.S. FDA required the boxed warning for all benzodiazepines to be updated, consistently describing risks of abuse, misuse, addiction, physical dependence, and withdrawal reactions.

*Common:* Sedation, euphoria, motor impairment.

*Less common:* Confusion, irritability and aggression, psychomotor agitation, lack of motivation, increased or loss of libido, impaired motor function, coordination, and balance, dizziness, cognitive impairments, hallucinations, short-term memory loss, and anterograde amnesia (common at higher doses). Some users report hangover-like symptoms (drowsiness, headaches, sluggishness, irritability) after taking it before sleep, likely due to its long half-life. Benzodiazepines reduce sleep quality by suppressing REM sleep, and rebound insomnia may occur upon discontinuation. They may also cause or worsen depression.

*Occasional:* Dysphoria, induction or increased frequency of seizures, and personality changes.