Depressants Clonazepam

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. 

The long-acting benzodiazepine clonazepam can be used as a first-line agent for those patients with particularly severe symptoms who are unable or unwilling to wait for the delayed therapeutic benefit of an antidepressant. Clonazepam can be initiated as a monotherapy for those without comorbid depression or in conjunction with an antidepressant for those who are also depressed. In the latter case, clonazepam can be used transiently with a plan to taper and discontinue it once sufficient time has elapsed to experience benefit from antidepressant therapy. 

Nearly all central nervous system depressants have some capacity to suppress seizures by virtue of their depressant activity on the brain and spinal cord. Clonazepam and diazepam are two benzodiazepines that depress epileptiform activity and are used in the treatment of epilepsy and seizure disorders (see Chapter 32). 

Other SSRIs may be selected as an alternative to fluvoxamine in the event that fluvoxamine cannot be used. Sertraline is the first option because of efficacy for pediatric GAD (Rynn et ah, 2001) paroxetine is an option because of controlled treatment data for adolescent depression (Keller et ah, 2000) and OCD (see Chapter 39) and fluoxetine is an option because of controlled treatment data for pediatric depression (Em-slie et ah, 1997). Eorazepam is included as a short acting alternative to clonazepam. Nortriptyline, which is less anticholinergic and thus may be better tolerated, is included as an alternative to IMF... 

Nevertheless, the GABAergic properties of benzodiazepines remain their most important clinical application. Over the past 30 years, the most widely used benzodiazepine drug has been diazepam (1.6). It is an anxiolytic, sedative, and muscle relaxant the anxious, depressed person becomes more outgoing and relaxed. There have been many diazepam analogs. Oxazepam (4.177) and lorazepam (4.178) have similar effects. Temazepam (4.179), flunitrazepam (4.180), and flurazepam (4.181) are useful sedative-hypnotics. Clonazepam (4.182) is a clinically useful anticonvulsant. Brotizolam (4.183), a novel benzodiazepine analog, seems to be an effective sedative-hypnotic. Midazolam (4.184) is an imidazolo-benzodiazepine that is water soluble and thus easily injectable. It is a hypnotic sedative with marked amnestic (i.e., memory loss) properties and is used in dentistry, endoscopic procedures, and induction to anesthetics in the elderly and in... 

BZDs may exacerbate depression and possibly increase suicide risk. Case reports and clinical trials also indicate that BZD treatment of generalized anxiety and panic may result in emergence of depression (215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225 and 226). In some of these reports, depression is ill-defined, but in others, it met DSM-III criteria for a major depressive disorder, requiring treatment with an antidepressant ( 225, 226). Depression has been reported with a variety of BZDs (alprazolam, bromazepam, clonazepam, diazepam, lorazepam), but there is no evidence that one is more likely than another to cause or aggravate depressive illness. 

The emergence of depressive symptoms, a phenomenon also reported with clonazepam and lorazepam (34, 35, 41, 42 and 43)... 

Like alprazolam, clonazepam may cause treatment-emergent depression in some patients. Pollack et al. (42) also reported that only 10% of their patients who remained on clonazepam had a history of depression, although 47% lost to follow-up and 30% who eventually required alternate treatment had histories of dysthymia or depression. Of 31 patients without a prior history of affective illness, depression developed in three on low daily dosages (0.75, 1.5, and 2 mg), one was switched to alprazolam, and the others responded to the addition of desipramine or imipramine. These investigators recommend that, until further data are available, PD patients with chronic or concurrent depression should not be given clonazepam alone and that those in whom depression develops during clonazepam therapy should have their dose lowered or an adjunctive antidepressant added. 

Some evidence indicates that clonazepam may induce depression more often than alprazolam. In a review of 177 patients given clonazepam and a matched number given alprazolam, Cohen and Rosenbaum (70) reported that depression developed in 5.5% of the clonazepam patients compared with only 0.7% of those on alprazolam. 

Given intravenously, both diazepam and midazolam are effective first-line treatments for status epilepticus. It is essential to be aware that the large doses that may be necessary to control convulsions are likely to cause respiratory depression and obtund protective reflexes. Oxygen and equipment suitable for its administration should be available. For intractable status epilepticus, clonazepam is a longer-acting alternative which can also be given by intravenous infusion. Overdosage... 

Benzodiazepines exert central depressant effects on spinal reflexes, in part mediated by the brainstem reticular system.3 For example, chlordiazepoxide depresses the duration of electrical after-discharge in the limbic system. Most benzodiazepines elevate the seizure threshold and therefore may be used as anticonvulsant medications. Diazepam, clonazepam, and clorazepate may be prescribed for this therapeutic purpose. 

Insomnia is a common comorbid condition with depression, and frequently is made worse by antidepressants, particularly the SSRIs. When insomnia persists despite adequate evaluation and attempts to reduce it by other approaches, it is often necessary to use a concomitant sedative-hypnotic, especially a short-acting nonbenzodiazepine with rapid onset such as zaleplon or zolpidem. At times a benzodiazepine sedative hypnotic such as triazolam or temazepam may be necessary. If anxiety persists during the day and cannot be otherwise managed, it may be necessary to add an anxiolytic benzodiazepine such as alprazolam or clonazepam. Use of sedative-hypnotics and anxiolytics should be short-term whenever possible. 

Further disruption of REM sleep is related to the presence of hallucinations and REM sleep behavior disorder in Parkinson s patients. A decrease in REM sleep has been associated with nocturnal hallucinations (125), and REM intrusion during daytime hallucinations has been reported (126). More than one third of Parkinson s patients also suffer from REM sleep behavior disorder (RBD) (127,128) or REM sleep without atonia (128). In these patients, there is also a significant reduction in total sleep time. In many cases RBD is diagnosed several years prior to the onset of Parkinson s disease (129), although a link between disease severity and duration and the presence of RBD has also been reported (128). RBD is most often treated with the administration of clonazepam (104,129). Patients with comorbid dementia and depression also experience a high level of sleep disturbance, associated with nocturnal vocalizations and hallucinations (130). One side effect of many antidepressant medications, however, is insomnia and sleep disturbance (131). 

Most of the sedative-hypnotics are capable of inhibiting the development and spread of epileptiform activity in the central nervous system. Some selectivity exists in that some members of the group can exert anticonvulsant effects without marked central nervous system depression (although psychomotor function may be impaired). Several benzodiazepines—including clonazepam, nitrazepam, lorazepam, and diazepam—are sufficiently selective to be clinically useful in the management of seizure states (see Chapter 24 Antiseizure Drugs). Of the barbiturates, phenobarbital and metharbital (converted to phenobarbital in the body) are effective in the treatment of generalized tonic-clonic seizures. 

Baldassano et al. (1996) described a depressed 18-year-old student who was started on paroxetine 20 mg/day and clonazepam 0.5 mg at night who developed worsening insomnia, a need to move about, restlessness, physical tiredness, and anxiety. The akathisia resolved on propranolol. The authors reviewed their charts and found 3 cases of akathisia among 67 patients (4%) treated with paroxetine. They concluded,... 

A 44-year-old man with depression was given hydroxyzine hydrochloride 100 mg/day, clonazepam 2 mg/ day, and citalopram 20 mg/day. Two years before he had tolerated fluoxetine for 6 months for an episode of depression, with good effect. After 7 weeks he developed weakness and weight loss. Physical examination was normal but the serum aspartate transaminase (AsT) was raised at 277 IU/L (reference range < 36 IU/1). His bilirubin was normal. Citalopram was withdrawn and the other drugs were continued intermittently 5 days later the serum aspartate transaminase had fallen by a half, and within 2 months it had returned to normal. 

A 17-year-old man with a 5-year history of severe depression took 120 tablets of ziprasidone 20 mg (2400 mg), 15-20 tablets of bupropion SR 150 mg (2250-3000 mg), 15 tablets of clonazepam 0.5 mg, and 4 tablets of lorazepam 0.5 mg (32). He was somnolent but responded to vocal commands. Over the next 45... 

Postmortem findings suggested severe nervous system and respiratory depression produced by high concentrations of clonazepam and oxycodone, including collapsed lungs, aspirated mucus, and heart failure. 

A 43-year-old man treated himself with a levamisole enema of 10 g (33 times the therapeutic dose) for a gastrointestinal worm infestation. Soon after he developed malaise, tachycardia, nausea, vertigo, and profuse diarrhea. He lost consciousness and developed generalized seizures and a respiratory arrest. He was intubated, ventilated, and treated with clonazepam. His condition improved after 4 hours. He remained somnolent for 6 hours, and was nauseated and vomited for 24 hours. There was hypokalemia after the diarrhea, raised creatine kinase activity, and a leukocytosis. An electrocardiogram showed ST depression. By the fourth day all his symptoms had subsided. 

A 60-year-old woman, with a history of hypertension, type 2 diabetes mellitus, and depression, took clomipramine 200 mg/day for 8 months and then 250 mg/day for 3 months. Her other medications were glibenclamide 7.5 mg/day, lisinopril 5 mg/day, and clonazepam 0.5 mg/day. Without any change in medications or other precipitants, she began to feel confused and weak. She became pyrexial (41.6°C), confused, and... 

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