THE SIDE AND WITHDRAWAL EFFECTS OF KLONOPIN (CLONAZEPAM)

I have been prescribed with klonopin for a total of about 3 years in the past, for anxiety. I am wondering whether this was responsible for some of my physical side effects (e.g. excess uric acid) which later combined with those from Epilim Crono.

Common[edit]

• Sedation^[33]
• Motor impairment

Less common[edit]

• Confusion^[5]
• Irritability and aggression^[34]
• Psychomotor agitation^[35]
• Lack of motivation^[36]
• Loss of libido
• Impaired motor function^[vague]
  • Impaired coordination
  • Impaired balance
  • Dizziness
• Cognitive impairments^[vague][37]
  • Hallucinations^[38]
  • Short-term memory loss^[39]
  • Anterograde amnesia (common with higher doses)^[40]
• Some users report hangover-like symptoms of drowsiness, headaches, sluggishness, and irritability upon waking up if the medication was taken before sleep. This is likely the result of the medication's long half-life, which continues to affect the user after waking up.^[41]

^[42][43] While benzodiazepines induce sleep, they tend to reduce the quality of sleep by suppressing or disrupting REM sleep.^[44] After regular use, rebound insomnia may occur when discontinuing clonazepam.^[45]

• Benzodiazepines may cause or worsen depression.^[5]

Occasional[edit]

• Dysphoria^[46]
• Thrombocytopenia^[47]
• Induction of seizures^[48][49] or increased frequency of seizures^[50]
• Personality changes^[51]
• Behavioural disturbances^[52]
• Ataxia^[5]

Rare[edit]

• Suicide through disinhibition^[6]
• Psychosis^[53]
• Incontinence^[54][55][56]
• Liver damage^[57]
• Paradoxical behavioural disinhibition^[5][58] (most frequently in children, the elderly, and in persons with developmental disabilities)
  • Rage
  • Excitement
  • Impulsivity

The long-term effects of clonazepam can include depression,^[5] disinhibition, and sexual dysfunction.^[59]

Drowsiness[edit]

Clonazepam, like other benzodiazepines, may impair a person's ability to drive or operate machinery. The central nervous system depressing effects of the drug can be intensified by alcohol consumption, and therefore alcohol should be avoided while taking this medication. Benzodiazepines have been shown to cause dependence. Patients dependent on clonazepam should be slowly titrated off under the supervision of a qualified healthcare professional to reduce the intensity of withdrawal or rebound symptoms.

Withdrawal-related[edit]

• Anxiety, irritability, insomnia, tremors
• Potential to exacerbate existing panic disorder upon discontinuation
• Seizures^[60] similar to delirium tremens (with long-term use of excessive doses)

Benzodiazepines such as clonazepam can be very effective in controlling status epilepticus, but, when used for longer periods of time, some potentially serious side-effects may develop, such as interference with cognitive functions and behavior.^[61] Many individuals treated on a long-term basis develop a dependence. Physiological dependence was demonstrated by flumazenil-precipitated withdrawal.^[62] Use of alcohol or other CNS depressants while taking clonazepam greatly intensifies the effects (and side-effects) of the drug.

A recurrence of symptoms of the underlying disease should be separated from withdrawal symptoms.^[63]

Tolerance and withdrawal[edit]

Main article: Benzodiazepine withdrawal syndrome

Like all benzodiazepines, clonazepam is a GABA-positive allosteric modulator.^[64][65] One-third of individuals treated with benzodiazepines for longer than four weeks develop a dependence on the drug and experience a withdrawal syndrome upon dose reduction. High dosage and long-term use increase the risk and severity of dependence and withdrawal symptoms. Withdrawal seizures and psychosis can occur in severe cases of withdrawal, and anxiety and insomnia can occur in less severe cases of withdrawal. A gradual reduction in dosage reduces the severity of the benzodiazepine withdrawal syndrome. Due to the risks of tolerance and withdrawal seizures, clonazepam is generally not recommended for the long-term management of epilepsies. Increasing the dose can overcome the effects of tolerance, but tolerance to the higher dose may occur and adverse effects may intensify. The mechanism of tolerance includes receptor desensitization, down regulation, receptor decoupling, and alterations in subunit composition and in gene transcription coding.^[5]

Tolerance to the anticonvulsant effects of clonazepam occurs in both animals and humans. In humans, tolerance to the anticonvulsant effects of clonazepam occurs frequently.^[66][67] Chronic use of benzodiazepines can lead to the development of tolerance with a decrease of benzodiazepine binding sites. The degree of tolerance is more pronounced with clonazepam than with chlordiazepoxide.^[68] In general, short-term therapy is more effective than long-term therapy with clonazepam for the treatment of epilepsy.^[69] Many studies have found that tolerance develops to the anticonvulsant properties of clonazepam with chronic use, which limits its long-term effectiveness as an anticonvulsant.^[70]

Abrupt or over-rapid withdrawal from clonazepam may result in the development of the benzodiazepine withdrawal syndrome, causing psychosis characterised by dysphoric manifestations, irritability, aggressiveness, anxiety, and hallucinations.^[71][72][73] Sudden withdrawal may also induce the potentially life-threatening condition, status epilepticus. Anti-epileptic drugs, benzodiazepines such as clonazepam in particular, should be reduced in dose slowly and gradually when discontinuing the drug to mitigate withdrawal effects.^[51] Carbamazepine has been tested in the treatment of clonazepam withdrawal but was found to be ineffective in preventing clonazepam withdrawal-induced status epilepticus from occurring.^[74]