Anticonvulsants withdrawal

Ketter TA, Malow BA, Flamini R, White SR, Post RM, Theodore WH. Anticonvulsant withdrawal-emergent psychopathology. Neurology 1994 44(1) 55-61. 

Most GCSE develops in patients with no history of epilepsy however, a patient with preexisting epilepsy may experience GCSE as a result of acute anticonvulsant withdrawal, metabolic disorder or concurrent illness, or progression of neurologic disease. 

Benzodiazepines. Several BZs have anticonvulsant activity and ate used for the treatment of epilepsy producing their anticonvulsant actions via interactions with the GABA /BZ receptor complex to enhance inhibitory GABAergic transmission (1). The anticonvulsant actions of the BZs tend to tolerate upon chronic usage in six months, and BZs also lead to withdrawal symptomatology. Other side effects include sedation, ataxia, and cognitive impairment. 

Promoting an Optimal Response to Therapy When administering an anticonvulsant, the nurse must not omit or miss a dose (except by order of the primary health care provider). An abrupt interruption in ther-apy by omitting a dose may result in a recurrence of the seizures. In some instances, abrupt withdrawal of an anticonvulsant can result in status epilepticus. 

Some of these drugp may have additional uses as sedatives, muscle relaxants, anticonvulsants, and in the treatment of alcohol withdrawal. For example, clo-razepate (Tranxene) and diazepam (Valium) are used as anticonvulsants (see Chap. 28). Additional uses of the individual antianxiety drugp are given in the Summary Drug Table Antianxiety Drugp. 

Control of early withdrawal symptoms, which prevents their progression to more serious symptoms, is the indication for which medications are most widely prescribed in the treatment of alcohol dependence. The most commonly used agents to treat alcohol withdrawal are the benzodiazepines, a class of drugs that, by virtue of their agonist activity at the GABA receptor complex, suppress the hyperexcitability associated with alcohol withdrawal. With widespread use of anticonvulsant medications for bipolar disorder and other disorders associated with behavioral disinhibition and CNS hyperexcitability, anticonvulsants have also been examined for use in the treatment of alcohol withdrawal. 

There are similarities between the biological actions of inhalants and those of alcohol and barbiturates (Bowen et al. 1996b). For example, acute administration of inhalants affects motor coordination (Moser and Balster 1981) and induces anxiolysis, whereas chronic administration is associated with physical dependence and withdrawal (Bowen et al. 1996a Evans and Balster 1991, 1993). In addition, some inhalant drugs have anticonvulsant properties (Wood et al. 1984). Like other CNS-depressant agents, inhalants have biphasic effects on spontaneous locomotor activity in rodents, with increased activity seen at lower doses and diminished locomotion seen at higher doses (Cause et al. 1985 Kjellstrand et al. 1985). 

Benzodiazepines are the evidence-based treatment of choice for uncomplicated alcohol withdrawal.17 Barbiturates are not recommended because of their low therapeutic index due to respiratory depression. Some of the anticonvulsants have also been used to treat uncomplicated withdrawal (particularly car-bamazepine and sodium valproate). Although anticonvulsants provide an alternative to benzodiazepines, they are not as well studied and are less commonly used. The most commonly employed benzodiazepines are chlordiazepoxide, diazepam, lorazepam, and oxazepam. They differ in three major ways (1) their pharmacokinetic properties, (2) the available routes for their administration, and (3) the rapidity of their onset of action due to the rate of gastrointestinal absorption and rate of crossing the blood-brain barrier. 

Cannabinoids appear to have a very complex interaction with seizure activity, exerting both anticonvulsant and proconvulsant effects. Anecdotal testimonies abound (Grinspoon and Bakalar, 1993), but there has been very little controlled human research. In single-case studies both use and withdrawal of marijuana have been linked to the resumption of seizures (Keeler and Reifler, 1967 Consroe et al., 1975). In a randomised placebo-controlled blind study, patients who responded poorly to standard treatments experienced improved seizure control in response to cannabidiol administration. Cannabidiol does not interact with cannabinoid receptors, and animal studies indicate that it has different anticonvulsant effects to other cannabinoids (Cunha et al., 1980). As such it may prove to have useful therapeutic properties. 

Alcohol withdrawal seizures do not require anticonvulsant drug treatment unless they progress to status epilepticus. Patients with seizures should be treated supportively. An increase in the dosage and slowing of the tapering schedule of the BZ used for detoxification or a single injection of a BZ may be necessary to prevent further seizure activity. 

Detoxification, as mentioned in Chapter 2, may involve the use of certain medications to prevent severe discomfort or even possible medical side effects related to withdrawal symptoms. These medicines can range from tranquilizers (often benzodiazepines) and antidepressants to anticonvulsives and antihypertensives, and the medical protocol for detox will depend on the drug or drugs being abused, the client s vital signs and other symptoms, and the known risk for certain withdrawal symptoms associated with the drugs being used. The duration... 

Diazepam (Valium, Diastat) [C-IVj [Anxiolytic, Skeletal Muscle Relaxant, Anticonvulsant, Sedative/Hypnotic/ Benzodiazepine] Uses Anxiety, EtOH withdrawal, muscle spasm, status epilepticus, panic disorders, amnesia, preprocedure sedation Action Benzodiazepine Dose Adults. Status epilepticus 5-10 mg IV/IM Anxiety 2-5 mg IM/IV Preprocedure 5-10 mg IV just prior to procedure Peds. Status epilepticus 0.5-2 mg IV/IM Sedation 0.2-0.5 mg/kg IV (onset w/in 5IV and 30 min IM duration about 1 h IV and IM) Caution [D, / -] Contra Coma, CNS depression, resp d es-sion, NAG, severe uncontrolled pain, PRG Disp Tabs 2, 5, 10 mg soln 1, 5 mg/mL inj 5 mg/mL rectal gel 2.5, 5, 10, 20 mg/mL SE Sedation, amnesia, bradycardia, i BP, rash, X resp rate Interactions T Effects W/ antihistamines, azole antifungals, BBs, CNS depressants, cimetidine, ciprofloxin, disulfiram, INH, OCP, omeprazole, phenytoin, valproic acid, verapamil, EtOH, kava kava, valman T effects OF digoxin, diuretics X effects w/ barbiturates, carbamazepine. 

Temazepam (Restoril) [C-IV] [Sedative/Hypnotic/ Benzodiazepine] Uses Insomnia, anxiety, depression, panic attacks Action Benzodiaz ine Dose 15-30 mg PO hs PRN X in elderly Caution [X, /-] Potentiates CNS dqjressive effects of opioids, barbs, EtOH, antihistamines, MAOIs, TCAs Contra NAG Disp Caps SE Confusion, dizziness, drowsiness, hangover Interactions T Effects W/ cimetidine, disulfiram, kava kava, valerian T CNS depression W/ anticonvulsants, CNS depressants, EtOH t effects OF haloperidol, phenytoin X effects W/ aminophylline, dyphylline, OCPs, oxtriphylline, rifampin, theophylline, tobacco X effects OF levodopa EMS Use caution w/ other benzodiazepines, antihistamines, opioids and verapamil, can T CNS depression concurrent EtOH can T CNS depression abruptly D/C after >10 d use may cause withdrawal OD May cause profound CNS depression, confusion, bradycardia, hypotension, and altered reflexes flumazenil can be used as antidote, activated charcoal may be effective... 

Note It is a good general practice to avoid treating the symptoms of use, withdrawal and overdose with other drugs. General support and control are often adequate. On the other hand the use of anticonvulsants should be prompt and the use of other drug supports considered carefully, in relationship to the clinical, psychological and social situation. 

It does not cause cognitive impairment and has a low potential for abuse. It does not show withdrawal reactions and has no anticonvulsive, hypnotic, muscle relaxant and sedative effects. The anxiolytic effect gradually evolves over 1-3 weeks, it does not potentiate the sedative effects of alcohol and is indicated for the short-term management of generalized anxiety disorder. 

Buspirone is as effective as the benzodiazepines in the treatment of general anxiety. However, the full anxiolytic effect of buspirone takes several weeks to develop, whereas the anxiolytic effect of the benzodiazepines is maximal after a few days of therapy. In therapeutic doses, buspirone has little or no sedative effect and lacks the muscle relaxant and anticonvulsant properties of the benzodiazepines. In addition, buspirone does not potentiate the central nervous system depression caused by sedative-hypnotic drugs or by alcohol, and it does not prevent the symptoms associated with benzodiazepine withdrawal. 

A long half-life is needed for a BZ to be effective as an anticonvulsant to avoid a withdrawal effect. Clonazepam, nitrazepam, and nordazepam are the BZs most often used for their anticonvulsant effects, al-... 

Buspirone does not appear to have a major effect on the BZ-GABA-chloride ionophore complex and, if anything, has some antagonistic interactions with GA-BAergic transmission (although it does not induce seizures) (Jann, 1988 Baldessarini, 1996). The lack of GABAergic effects is evident in the fact that buspirone does not consistently cause sedation, it is not a muscle relaxant, it is not an anticonvulsant, and it does not relieve BZ withdrawal (Jann, 1988 Cole and Yonkers, 1995). 

---