Clonazepam adverse effects

As with the barbiturates, the most common adverse reaction seen with the use of clonazepam (Klonopin), clorazepate (Tranxene), and diazepam (Valium) is sedation in varying degrees. Additional adverse effects may include anorexia, constipation, or diarrhea. Some adverse reactions are dose dependent, whereas others may diminish in intensity or cause few problems after several weeks of therapy. 

Clonazepam is the most extensively studied BZ for treatment of generalized SAD. It improved fear and phobic avoidance, interpersonal sensitivity, fears of negative evaluation, and disability measures. Adverse effects include sexual dysfunction, unsteadiness, dizziness, and poor concentration. Clonazepam should be tapered at a rate not to exceed 0.25 mg every 2 weeks. 

Clonazepam Klonopin Tablet 0,5, 1,2 mg 0.5-20 mg/day in divided doses or one dose at bedtime. Dosage should be slowly adjusted up and down according to response and adverse effects. 

Typical doses of clonazepam have been in the range of 2 to 16 mg/day given on a once or twice per day schedule due to its longer half-life. A major advantage of this anticonvulsant is its relative lack of adverse effects and freedom from laboratory monitoring in comparison with CBZ and VPA. Clonazepam may be more useful when combined with lithium or CBZ rather than as a specific antimanic agent, perhaps supplanting the need for antipsychotics. In this sense, it can be viewed as a behavioral suppressor, rather than a true mood stabilizer (121). 

Interestingly, 10 patients (50%) had discontinued clonazepam at follow-up because of adverse effects, inadequate response, or preference for a previously used treatment. 

Adverse Effects Sedation is the most prominent initial effect of clonazepam, usually subsiding in 2 to 3 days, but may persist in some patients. Other reported effects include the following ... 

In their long-term follow-up study. Pollack et al. ( 42) found that five patients had stopped clonazepam because of adverse effects (dysthymia, one irritability, two nausea and sedation, two) and that four patients required dose reductions because of adverse effects (predominantly sedation). 

At least three drugs are effective against absence seizures. Two are nonsedating and therefore preferred ethosuximide and valproate. Clonazepam is also highly effective but has disadvantages of dose-related adverse effects and development of tolerance. Lamotrigine and topiramate may also be useful. 

If these measures fail, clonidine, fluphenazine, clonazepam, or carbamazepine should be tried. The pharmacologic properties of these drugs are discussed elsewhere in this book. Clonidine reduces motor or vocal tics in about 50% of children so treated. It may act by reducing activity in noradrenergic neurons in the locus coeruleus. It is introduced at a dose of 2-3 mcg/kg/d, increasing after 2 weeks to 4 mcg/kg/d and then, if required, to 5 mcg/kg/d. It may cause an initial transient fall in blood pressure. The most common adverse effect is sedation other adverse effects include reduced or excessive salivation and diarrhea. Phenothiazines such as fluphenazine sometimes help the tics, as do dopamine... 

Clobazam, a 1,5-benzodiazepine, differs in its chemical structure from most other benzodiazepines. It has been claimed to have less sedative effects for its effective anticonvulsant and anti-anxiety effects (SED-12, 98). Whether because of tolerance or not, clobazam tends to be less sedative than clonazepam. Both the therapeutic and adverse effects of clobazam have been related to its major metabolite Al-desmethylclobazam, the formation of which depends on CYP2C19 activity. Mutant alleles that confer high CYP2C19 activity, and are therefore associated with high concentrations of the metabolite, are particularly common (30-40%) in Asian populations (1)-... 

In controlled trials with clonazepam, adverse events were recorded in 60-90% of cases, and led to withdrawal rates as high as 36% (8). The most common effects were drowsiness, ataxia, and behavioral and personality changes. Other problems were hypersalivation, tolerance, and sometimes a paradoxical increase in seizure frequency. 

Withdrawal effects can be troublesome. Of 13 patients taken off clonazepam 0.01-0.5 mg/day because of adverse effects, 8 had withdrawal seizures and 5 had other withdrawal symptoms (SEDA-19, 63). Choreoathetosis was described in one patient completing withdrawal of clonazepam (SED-13,152). 

Clonazepam is widely used for the treatment of sleep disturbances related to post-traumatic stress disorder, despite very limited published data supporting its use for this indication. In a randomized, single-blind, placebo-controlled, crossover trial of clonazepam 1 mg at bedtime for 1 week followed by 2 mg at bedtime for 1 week in six patients with combat-related post-traumatic stress disorder there were no statistically significant differences between clonazepam and placebo (4). Adverse effects of clonazepam were generally mild and essentially indiscernible from those attributed to placebo. Only one patient elected to continue taking clonazepam at the end of the trial. The small sample size was a significant limitation of the study. 

Behavioral adverse events associated with clonazepam include agitation, aggression, hyperactivity, irritability, property destruction, and temper tantrums. These adverse effects can be inadvertently confused with other behavioral or psychiatric conditions, especially if exacerbation of existing challenging behavior occurs. 

BZs should be reserved for patients at low risk of substance abuse, those who require rapid relief, or those who have not responded to other therapies. Clonazepam is the most extensively studied BZ for treatment of generalized SAD. It improved fear and phobic avoidance, interpersonal sensitivity, fears of negative evaluation, and disability measures. Adverse effects include sexual dysfunction, unsteadiness, dizziness, and poor concentration. Clonazepam should be tapered at a rate not to exceed 0.25 mg every 2 weeks. Gabapentin was effective for SAD, and onset of effect was 2 to 4 weeks. j8-Blockers blunt the peripheral autonomic symptoms of arousal (e.g., rapid heart rate, sweating, blushing, and tremor) and are often used to decrease anxiety in performance-related situations. For specific SAD, 10 to 80 mg of propranolol or 25 to 100 mg of atenolol can be taken 1 hour before the performance. A test dose should be taken at home on a day before the performance to be sure adverse effects wUl not be problematic. Incomplete response to a first-line agent may benefit from augmentation with buspirone or clonazepam. 

What are the most frequently seen adverse effects to clonazepam therapy ... 

Clonazepam is well absorbed, 95 to 98% protein bound, and extensively metabolized by CYP3A4. Clonazepam displays a wide spectrum of antiseizure activities and is one of the most potent AEDs. Side effects are common, however, and the development of tolerance is more frequent than with ethosuximide or valproate. Sedation is prominent, especially early in treatment. Drowsiness, ataxia, and behavioral changes may be disabling, but slowly Increasing its dose over a 2-week period Is recommended to minimize adverse effects. Diplopia, headaches, nystagmus, and other neurologic effects have been reported with the use of clonazepam. 

None of the interactions between the benzodiazepines and antiepileptics described here appear to be of major clinical importance, with the possible exception of the interaction between clobazam and felbamate. If both drugs are given be aware that additive sedative or other adverse effects may occur. This may also be possible in some rare cases with chlordiazepoxide or clobazam and phenobarbital clonazepam and lamotrigine or primidone and clorazepate and primidone. 

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