Clonazepam abuse

Frauger E, Pauly V, Thirion X, Natali F, Pradel V, Reggio P, Rouby F, Coudert H, Micallef J. Estimation of clonazepam abuse liability a new method using a reimbursed drug database. Int Clin Psychopharmacol 2009 24(6) 318-24. 

Anxiety disorders are common in the population of opioid-addicted individuals however, treatment studies are lacking. It is uncertain whether the frequency of anxiety disorders contributes to high rates of illicit use of benzodiazepines, which is common in methadone maintenance programs (Ross and Darke 2000). Increased toxicity has been observed when benzodiazepines are co-administered with some opioids (Borron et al. 2002 Caplehorn and Drummer 2002). Although there is an interesting report of clonazepam maintenance treatment for methadone maintenance patients who abuse benzodiazepines, further studies are needed (Bleich et al. 2002). Unfortunately, buspirone, which has low abuse liability, was not effective in an anxiety treatment study in opioid-dependent subjects (McRae et al. 2004). Current clinical practice is to prescribe SSRIs or other antidepressants that have antianxiety actions for these patients. Carefully controlled benzodiazepine prescribing is advocated by some practitioners. 

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. 

High-potency benzodiazepines (e.g., clonazepam and lorazepam) are common alternatives to or in combination with antipsychotics for acute mania, agitation, anxiety, panic, and insomnia or in those who cannot take mood stabilizers. Lorazepam IM may be used for acute agitation. A relative contraindication for long-term benzodiazepines is a history of drug or alcohol abuse or dependency. 

The most commonly ingested BZs by individuals seen in emergency rooms are alprazolam and clonazepam, but lorazepam and diazepam are also commonly abused. 

Because Rohypnol is banned in the United States, there is an emerging trend for young people to start abusing two other Rohypnol-like drugs that are still legal in the United States clonazepam (Klonopin ) and alprazolam (Xanax). Both Klonopin and Xanax are benzodiazepines that are used for the treatment of anxiety and insomnia. Although they are less potent than Rohypnol, they can produce similar effects when mixed with alcohol and also have been reported to enhance the effects of heroin. 

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. 

Alprazolam has been researched more extensively than any other benzodiazepine in panic disorder, and is very effective. Because of its short duration of action, it generally must be administered in three to five daily doses. Clonazepam, which has a longer duration of action than alprazolam, has also been investigated in panic disorder. It can generally be administered twice a day. Clonazepam is reported to have less abuse potential than alprazolam and to be easier to taper during discontinuation owing to its longer half-life. 

The drugs in Schedule IV have a relatively low abuse potential and risk for psychological or physical dependence relative to those listed in Schedule in and include such drugs as barbital, phenobarbital, methylphe-nobarbital, chloral betaine (Beta Chlor), chloral hydrate, ethchlorvynol (Placidyl), ethinamate (Valmid), meprobamate (Equanil, Miltown), paraldehyde, methohexital, fenfluramine, diethyipropion, phentermine, chlor-diazepoxide (Librium), diazepam (Valium), oxazepam (Serax), clorazepate (Tranxene), flurazepam (Dalmane), clonazepam (Clonopin), prazepam (Verstran), lorazepam (Ativan), mebutamate, and dextropropoxyphene (Dar-von). 

A 38-year-old white woman was found dead (15). She had physical evidence of previous drug abuse and positive hepatitis B and C serology. Her plasma clonazepam concentration was 1.41 pg/ml and her plasma oxycodone concentration was 0.60 pg/ml. 

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. 

If clonazepam can be considered a long-acting alprazolam-like anxiolytic , then alprazolam XR can be considered an even longer-acting clonazepam-like anxiolytic with the potential of improved tolerability features in terms of less euphoria, abuse, dependence, and withdrawal problems, but this has not been proven... 

For the acute relief of anxiety or panic attacks, benzodiazepines are often useful, usually on an as-needed basis. Many clinicians are reluctant to prescribe these medications for an extended period of time (due to risks associated with physiologic dependence, withdrawal, or abuse), but for the relief of acute symptoms, benzodiazepines are a valuable therapeutic modality. Although a wide variety of benzodiazepines are currently available, they are all qualitatively similar in terms of their pharmacologic effects and side effect potential. Clonazepam and alprazolam are the two benzodiazepines used most commonly to treat anxiety disorders. 

Pharmacologic treatment of RLS includes dopaminergic agents, benzodiazepines, opioids, or anticonvulsants. In mild cases of RLS, benzodiazepines may be first-line agents. Clonazepam, lorazepam, triazolam, and temazepam have been effective. Clonazepam 0.5 to 2 mg is most frequently studied. Opiates such as methadone 5 to 20 mg, codeine 30 to 120 mg, and oxycodone 2.5 mg are very effective, but the development of tolerance is a concern. Abuse potential with opiates is also a concern due to the chronic nature of the condition. Other agents that have been used include apomorphine, amantadine, tramadol, magnesium, oxycodone, propoxyphene, gabapentin, bromocriptine, clonidine, and carbamazepine. Tolerance may de-... 

Anxiety states Benzodiazepines with intermediate or long durations of action are favored in the drug treatment of most anxiety states. Alprazolam and clonazepam have greater efficacy than other benzodiazepines in panic and phobic disorders. The anxiolytic effects of buspirone occur without sedation or cognitive impairment but take a week or more to develop. Buspirone is commonly used for generalized anxiety disorders in patients with a past history of substance abuse. 

There is a report of seizures, unsteady gait and blurred speech in a patient with bipolar disorder and cystic fibrosis taking lithium and paroxetine both drugs were discontinued. However, this patient was abusing oxycodone and clonazepam and was also on a variety of anti-asthma medications (salbutamol, salmeterol, budesonide, montelukast and cromoglicate), so the exact cause of the seizures is unclear. ... 

Drug abuse Clonazepam is often used as a drug of abuse and to treat drug addicts. In cases referred to the Section of Forensic Chemistry at the University of Copenhagen in 2002-2007 clonazepam and its metabolite 7-aminoclonazepam were detected in 297 cases after traffic accidents (median 0.067 mg/kg), in 92 perpetrators or victims of a crime (median 0.071 mg/kg), and in 140 postmortem cases (median 0.115 mg/kg) [10. In 27 of the postmortem cases with high concentrations other drugs had been taken, but clonazepam was thought to have been the primary cause of death in five (concentrations 0.26-0.54 mg/kg). 

The extent of abuse of clonazepam has been assessed in a French study, in which deliveries of clonazepam to individuals who had had a prescription reimbursed were monitored for 9 months [11 ]. There was an increase of 82% in participants who had a delivery of clonazepam between 2001 and 2006, and some deviant participants were identified they included a higher proportion of men, benzodiazepine users, and buprenorphine users. The proportion of deviant participants increased between 2001 and 2006 from 0.86% to 1.38%. 

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