Clonazepam long-term effects

Lithium may facilitate the release of 5-HT, perhaps by increasing tryptophan uptake, enhancing 5-HT release through presynaptic autoreceptors, and/or by increasing activity at postsynaptic 5-HT receptors (i.e., act as a 5-HT agonist). Some data, however, question the long-term effect of lithium on 5-HT enhancement when studied in patients, as opposed to healthy control subjects ( 27). Similar to lithium, clonazepam can increase 5-HT synthesis and cerebrospinal fluid (CSF) levels of its major metabolite, 5-hydroxyindoleacetic acid. Other agents known to enhance 5-HT activity by different mechanisms have also shown initial promise as potential antimanic treatments (e.g., L-tryptophan, a 5-HT precursor). 

Benzodiazepines are used commonly in SAD however, there are limited data supporting their use. Clonazepam has been effective for social anxiety, fear, and phobic avoidance, and it reduced social and work disability during acute treatment.58 Long-term treatment is not desirable for many SAD patients owing to the risk of withdrawal and difficulty with discontinuation, cognitive side effects, and lack of effect on depressive symptoms. Benzodiazepines may be useful for acute relief of physiologic symptoms of anxiety when used concomitantly with antidepressants or psychotherapy. Benzodiazepines are contraindicated in SAD patients with alcohol or substance abuse or history of such. 

Benzodiazepines. The best studied of the benzodiazepines for social anxiety disorder, clonazepam has been demonstrated in controlled trials to be effective during both acute treatment (at an average dose of 2.4mg/day) and long-term maintenance therapy lasting up to 2 years. A controlled study of another high potency benzodiazepine, alprazolam, also proved effective, though it was outperformed by the MAOI antidepressant phenelzine and exhibited response rates lower than those reported with clonazepam. 

Benzodiazepines. Longer-acting clonazepam and shorter-acting alprazolam have also been used in the treatment of social anxiety disorder, and controlled trials have shown them to be quite effective. In our experience, alprazolam is best suited for discrete periods of intermittent anxiety, though both clonazepam and the new long-acting alprazolam (Xanax XR) are likely effective for long-term treatment. 

Benzodiazepines are the drugs of choice for status epilepticus (see above) however, development of tolerance renders them less suitable for long-term therapy. Clonazepam is used for myoclonic and atonic seizures. Clobazam, a 1,5-benzodiazepine exhibiting an increased anticonvulsant/seda-tive activity ratio, has a similar range of clinical uses. Personality changes and paradoxical excitement are potential side effects. 

The speciflc clinical use of the numerous available benzodiazepines depends on their individual pharmacokinetic and pharmacodynamic properties. Drugs with a high affinity for the GABAa receptor (alprazolam, clonazepam, lorazepam) have high anxiolytic efficacy drugs with a short duration of action (temazepam) are used as hypnotics to minimise daytime sedative effects. Diazepam has a long half-life and duration of action and may be favoured for long-term use or when there is a history of withdrawal problems oxazepam has a slow onset of action and may be less susceptible to abuse. 

Davidson JRT, Eord SM, Smith RD, et al Long-term treatment of social phobia with clonazepam. J Clin Psychiatry 52 (suppl) 16-20, 1991b Davidson JRT, Potts N, Richichi E, et al Treatment of social phobia with clonazepam and placebo. J Clin Psychopharmacol 13 423-428, 1993 Davies P Theoretical treatment possibilities for dementia of the Alzheimer type the cholinergic hypothesis, in Strategies for the Development of an Effective Treatment for Senile Dementia. Edited by Crook T, Gershon S. New Canaan, CT, Mark Powley Associates, 1981, pp 19-32... 

Long-Term Efficacy Clonazepam has been shown to be effective for long-term use to manage PD or agoraphobia with panic attacks. In a 1-year follow-up study of clonazepam for PD or agoraphobia with panic attacks. Pollack et al. (42) reported that 18 of 20 (90%) patients, many of whom had failed to respond to or tolerate other BZDs or antidepressants, maintained a good response. One patient was in complete remission at 44 weeks and remained well even off medication at 56 weeks. Tolerance to therapeutic efficacy did not appear to develop, although 40% required a dose increase (from 0.25 to 4.5 mg) to maintain initial improvement. 

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). 

Clonazepam has been shown to be effective for long-term therapy without development of tolerance as manifested by dose escalation or worsening of clinical status (77). Daily doses of 1 to 2 mg offer the best balance of therapeutic benefit and tolerability ( 78). 

Several members of the benzodiazepine group are effective in treating epilepsy, but most are limited because of problems with sedation and tolerance. Some agents such as diazepam (Valium) and lorazepam (Ativan) are used in the acute treatment of status epilepti-cus (see Treatment of Status Epilepticus ), but only a few are used in the long-term treatment of epilepsy. Clonazepam (Klonopin) is recommended in specific forms of absence seizures (e.g., the Lennox-Gastaut variant) and may also be useful in minor generalized seizures such as akinetic spells and myoclonic jerks. Clorazepate (Tranxene) is another benzodiazepine that is occasionally used as an adjunct in certain partial seizures. 

Psychological Effects of long-term (2.75 1.62 years) use of clonazepam 0.5-1 mg on nonrapid eye movement (NREM) sleep patterns in rapid eye movement sleep behaviour disorder were evaluated in 46 participants [8 ]. The patients had the following diagnoses 15 with idiopathic rapid eye movement sleep behaviour disorder (iRBD), 13 with narcolepsy/RBD and 18 normal controls. The study found that clonazepam modifies some aspects of NREM sleep in iRBD patients witii a decrease in its instability. The authors concluded that a complex modification of sleep chin atonia exists in iRBD patients, which also involves NREM sleep. The result of this study should be interpreted with caution, as the design of the study was not clear, some participants were recruited retrospectively, and the sample size was small. 

Ferri R, Zucconi M, MareUi S, Plazzi G, Schenck CH, Ferini-Strambi L. Effects of long-term use of clonazepam on nonrapid eye movement sleep patterns in rapid eye movement sleep behavior disorder. Sleep Med May 2013 14(5) 399-406. 

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