Акатизия при отмене габапентина

OBJECTIVE: To report a case of akathisia in a patient with type 2 diabetes after abrupt discontinuation of gabapentin.

CASE SUMMARY: A 76-year-old female with type 2 diabetes was admitted for change in mental status, agitation, and restless limb movements. She had been taking gabapentin 3600 mg daily for approximately 1 month for diabetic neuropathy. Her other home medications were glyburide 10 mg twice daily, oxycodone/acetaminophen 5 mg/325 mg every 6 hours as needed for leg pain, and zolpidem 5 mg at bedtime. She had taken none of these drugs for 4 days prior to admission because she was unable to have the prescriptions refilled. Subsequently, the patient exhibited repeated arm and leg motions in response to an inner restlessness. Upon admission to the emergency department, she was agitated and restless; all vital signs and results of laboratory studies were within normal limits. Gabapentin was restarted at the original dosage and the symptoms resolved within 8 hours. Because the patient developed lethargy, the gabapentin dosage was reduced and titrated to the original level over 2 days. After 3 days, the patient was well oriented and experienced no further symptoms. She was discharged on the original dosage of gabapentin.

DISCUSSION: To our knowledge, this is the first reported cases of akathisia induced by gabapentin withdrawal. Available case reports suggest that gabapentin withdrawal can occur at doses ranging from 400-8000 mg/day. Patients experienced symptoms similar to those that develop with benzodiazepine withdrawal and were taking gabapentin for as little as 3 weeks to as long as 5 years. This is the first case report to describe akathisia induced by gabapentin withdrawal. The Naranjo probability scale revealed a probable relationship between akathisia and gabapentin withdrawal.

CONCLUSIONS: If gabapentin discontinuation is desired, it is prudent to gradually taper the dose to avoid withdrawal symptoms, which may occur after as little as 1 month of treatment. Should the patient experience withdrawal symptoms, the optimal treatment is to restart gabapentin.

Akathisia Induced by Gabapentin Withdrawal

Evidence supporting antiepileptics for mood disorders and schizophrenia

Medication	Bipolar disorder			Major depressive disorder	Schizophrenia
	Mania	Depression	Maintenance
Carbamazepine					(aggression, impulsivity)
Lamotrigine					(adjunct to clozapine)
Valproate					(aggression, impulsivity)
Gabapentin
Levetiracetam
Oxcarbazepine
Tiagabine
Topiramate
Zonisamide
	: strong evidence supporting efficacy;
	: moderate evidence supporting efficacy;
	: weak evidence supporting efficacy
Source: For an extensive bibliography of studies that support these recommendations, see this article at CurrentPsychiatry.com

Table 2
Off-label use of antiepileptics for various psychiatric disorders

Condition/disorder	Possible medication(s)*
Alcohol withdrawal/relapse prevention	Carbamazepine, topiramate, valproate
Benzodiazepine withdrawal	Carbamazepine, valproate
Binge eating disorder	Topiramate, zonisamide
Bulimia nervosa	Topiramate
Drug dependence/abstinence	Carbamazepine, lamotrigine, topiramate, tiagabine
Generalized anxiety disorder	Pregabalin, tiagabine
Obesity	Lamotrigine, topiramate, zonisamide
Panic disorder	Valproate
Posttraumatic stress disorder	Lamotrigine
Social phobia	Gabapentin, pregabalin
* Based on small randomized controlled trials, open-label trials, or case reports. Further investigation in large systematic trials is needed

Explain to patients taking topiramate or zonisamide that increasing their fluid intake will significantly reduce kidney stone risk

The FDA recently announced a warning of a risk of aseptic meningitis with lamotrigine.11 In 40 reported cases, symptoms—headache, fever, nausea, vomiting, nuchal rigidity, rash, photophobia, and myalgias—occurred between 1 and 42 days of treatment and typically resolved after lamotrigine was withdrawn. In 15 patients in whom lamotrigine was re-initiated, meningitis symptoms returned quickly and with greater severity.

Antiepileptics for psychiatric illness: Find the right match

Once-Daily Gabapentin Effective for Postherpetic Neuralgia Pain and Sleep Disturbance

Прегабалин: злоупотребление, зависимость, синдром отмены

Pregabalin is a GABA-analog that selectively binds to the alpha2 delta subunit of voltage-gated calcium channels. It inhibits the release of excitatory neurotransmitters and increases neuronal GABA levels. Like some other compounds that modulate GABA-ergic neurotransmission, pregabalin might have a potential for abuse. Our patient had a history of drug addiction, which may be important in the reward effect of pregabalin. We therefore recommend being especially cautious when using pregabalin to treat patients with a history of drug or alcohol dependence.

Pregabalin Abuse, Dependence, and Withdrawal: A Case Report

Pittenger C, Desan PH: Gabapentin abuse, and delirium tremens upon gabapentin withdrawal. J Clin Psychiatry 2007

Vicctorio-Vigneau C, Guerlais M, Jolliet P: Abuse, dependency and withdrawal with gabapentin: a first case report

Потенциирование, добавление второго антипсихотика или повышение доз атипичных антипсихотиков

The atypical antipsychotics risperidone, olanzapine, quetiapine, ziprasidone,and aripiprazole have become first-line treatment for schizophrenia because they reduce the positive symptoms of psychosis but do not have a high incidence of extrapyramidal symptoms. However, these agents, like other antipsychotics, may take as long as 16 or more weeks to produce a response, and even with prolonged treatment are unlikely to evoke responses greater than 50% improvement in symptoms. This has led to the experimental use of high atypical antipsychotic doses, antipsychotic polypharmacy, and augmentation with other psychotropic drugs, all of which occur commonly in clinical practice. This article reviews the current evidence for these increasingly common means of treating
schizophrenia and psychosis, with particular emphasis on polypharmacy and augmentation. To date, there are only two controlled studies of antipsychotic polypharmacy involving an atypical antipsychotic; the rest of the data are uncontrolled trials and case reports that describe a mixture of positive and negative findings. One multicenter, double-blind trial shows a faster onset of action when divalproex is added to risperidone or olanzapine than with antipsychotic monotherapy. A small double-blind study demonstrates efficacy when lamotrigine is added to clozapine. The rest of the data on augmentation with anticonvulsants are uncontrolled, and most report adverse effects. With the exception of divalproex, there are currently no compelling data to justify the use of antipsychotic polypharmacy or augmentation. Existing evidence suggests that the best treatments for schizophrenia and psychosis may be long-term trials of a sequence of atypical antipsychotic monotherapies at therapeutic doses.

Increasing the dose in patients with partial responses or breakthrough symptoms is faster and easier than switching to another agent, and it is possible that it would result in improved efficacy. There are also some patients who may be
rapid metabolizers, and thus require higher doses than the average patient. However, although some patients may benefit from higher doses, this method of treatment can
increase the risk of side effects, especially motor side effects. Positron emission tomography (PET) data demonstrate that dopamine 2 (D2) receptor occupancy of 70% is necessary for therapeutic benefits, while occupancy greater than 80% is associated with extrapyramidal symptoms [34]. Doses at the upper end of the recommended range for the first-line antipsychotics may already result in 80% occupancy of D2
receptors in the nigrostriatal pathway [35], so that doses above those ranges are more likely to induce EPS. In particular, the risk of EPS with risperidone is dose-
dependent and may even increase above 4 mg/day

In summary, there is currently no compelling evidence to support long-term antipsychotic polypharmacy. There are few theoretical benefits and many theoretical detriments. Although individual patients may respond to antipsychotic
polypharmacy without side effects, adequate trials have not yet determined the costs versus the benefits of this option.

The evidence for augmentation of atypical antipsychotics varies depending on the particular agent. Controlled studies with conventional antipsychotics suggest that augmentation with benzodiazepines is most likely useful as an acute treatment for patients with agitation and hostility, but controlled studies do not exist for atypical antipsychotics. As mentioned earlier, a multicenter double-blind study demonstrates the safety and efficacy of only one augmenting agent in schizophrenia, namely divalproex [96]. Controlled studies combining divalproex and an atypical antipsychotic also show additive benefits in bipolar disorder, strengthening the appeal of this particular augmenting strategy [167-168]. Unfortunately, there are no controlled data for augmentation of atypical antipsychotics with other anticonvulsants even though this is a frequent and expensive practice, especially with gabapentin. Thus, the evidence currently suggests that divalproex is perhaps the best evidence-based augmentation option when multiple monotherapies fail

A Critical Review of Atypical Antipsychotic Utilization: Comparing
Monotherapy with Polypharmacy and Augmentation

Антиконвульсанты в терапии поведенческих и психологических симптомов деменции

"INTRODUCTION: Dementia, besides the dominant cognitive disorders that define it, is associated with behavioral disturbances, the consequences of which are, on various levels, a determining factor for the handling of these patients. The treatment of behavioral and psychological symptoms is essential and although, to date, no therapeutic solution is satisfactory, it is necessary to look for an alternative to the neuroleptics usually employed, which raise real problems of tolerance in this geriatric population. BACKGROUND: For several years, anticonvulsants, among which some have shown mood stabilizing activity, have been the object of research in this indication. The purpose of this review of the literature is to assess the interest and the limits of anticonvulsant mood stabilizers (carbamazepine, valproic acid, gabapentin, lamotrigine, topiramate, oxcarbazepine) in the treatment of the so-called "noncognitive" symptoms of dementia. Their mechanism of action in mood disorders is not well known, but it would appear to be via the modulation of glutamate-mediated excitatory synaptic transmission and gamma-aminobutyric acid (GABA)-mediated inhibitory synaptic transmission that anticonvulsants might reduce behavioral symptoms in demented patients. METHODS: The method employed in this work was a systematic bibliographic review, in which only the double-blind placebo-controlled studies or the clinically detailed enough open-labelled studies using validated scales were retained. RESULTS: Among these medications, only carbamazepine demonstrated its efficacy in behavioral and psychological symptoms of dementia (BPSD) in controlled studies, notably that of Tariot et al. [J Am Geriatr Soc 42 (1994) 1160-1166 and Am J Psychiatry 155 (1998) 54-61] and Olin et al. [Am J Geriatr Psychiatry 9 (2001) 400-405], but with significant adverse events (sedation, hyponatremia, cardiac toxicity), particularly in the elderly and, being a strong enzymatic inducer, with a high likelihood of drug-drug interactions. Valproic acid showed some interesting results in BPSD within a large number of open studies and case reports. However, among the five controlled studies that have been published [Curr Ther Res 62 (2001) 51-67; Am J Geriatr Psychiatry 9 (2001) 58-66; Int J Geriatr Psychiatry 17 (2002) 579-585; Curr Alzheimer Res 2 (2005) 553-558 and Am J Geraitr Psychiatry 13 (2005) 942-945], none confirmed its efficacy on these symptoms. Regarding its tolerability in the geriatric population, no notable major side effect was reported (haematologic and hepatic effects are not more frequent than in the general population), except possible excessive sedation. Moreover, it appears that valproic acid could have neuroprotective effects, even if the contrary has been observed in a recent study. More studies need to be (and are being) conducted, notably on the interest of valproic acid in prophylaxis of BPSD. Gabapentin seems to be worthwhile and well tolerated in this indication, but no controlled study has been conducted to prove its efficacy, even if a quite important number of case reports and open studies have shown encouraging results. Concerning lamotrigine, which may potentially induce severe cutaneous side effects when administered with valproic acid, this drug has shown its efficacy in bipolar disorders and two recent case reports seem to indicate some interest in BPSD. Furthermore, lamotrigine appears to have neuroprotective effects. Although topiramate has shown interesting results in one open study in BPSD, its use in demented patients cannot be recommended because of its deleterious effect on cognitive functions. Oxcarbazepine, theoretically, could be an alternative to carbamazepine, which is, as aforesaid, the only anticonvulsant that proved its interest in BPSD. However, no clinical study has yet been published to support this hypothesis. This drug is better tolerated than carbamazepine, but induces severe and more frequent hyponatremia. DISCUSSION AND CONCLUSION: Finally, although we all know that antipsychotics should no longer be prescribed in the elderly, the treatment of behavioral and psychological symptoms of dementia remains a difficult problem, considering the lack of a real alternative to these medications. Anticonvulsant mood stabilizers are an interesting solution but none of them, other than carbamazepine, which did, but which is not better tolerated than the usual drugs in this population - was able to prove its efficacy in this indication. Among these medications, valproic acid, gabapentin and lamotrigine should be studied further, and the neuroprotective effect of some of them is an interesting route for research."

Anticonvulsant mood stabilizers in the treatment of behavioral and psychological symptoms of dementia (BPSD)

Влияние современных антиконвульсантов на когнитивные функции

"BACKGROUND: Antiepileptic drugs (AEDs) can be associated with neurotoxic side effects including cognitive dysfunction, a problem of considerable importance given the usual long-term course of treatment. Pregabalin is a relatively new AED widely used for the treatment of seizures and some types of chronic pain including fibromyalgia. We measured the cognitive effects of 12 weeks of pregabalin in healthy volunteers. METHODS: Thirty-two healthy volunteers were randomized in a double-blind parallel study to receive pregabalin or placebo (1:1). Pregabalin was titrated over 8 weeks to 600 mg/d. At baseline, and after 12 weeks of treatment, all subjects underwent cognitive testing. Test-retest changes in all cognitive and subjective measures were Z scored against test-retest regressions previously developed from 90 healthy volunteers. Z scores from the placebo and pregabalin groups were compared using Wilcoxon tests. RESULTS: Thirty subjects completed the study (94%). Three of 6 target cognitive measures (Digit Symbol, Stroop, Controlled Oral Word Association) revealed significant test-retest differences between the pregabalin and placebo groups, all showing negative effects with pregabalin (p < 0.05). These cognitive effects were paralleled by complaints on the Portland Neurotoxicity Scale, a subjective measure of neurotoxicity (p < 0.01). CONCLUSION: At conventional doses and titration, pregabalin induced mild negative cognitive effects and neurotoxicity complaints in healthy volunteers. These effects are one factor to be considered in the selection and monitoring of chronic AED therapy. Class of Evidence: This study provides Class I evidence that pregabalin 300 mg BID negatively impacts cognition on some tasks in healthy volunteers."

Cognitive effects of pregabalin in healthy volunteers: a double-blind, placebo-controlled trial.

"OBJECTIVE: To evaluate the cognitive effects of topiramate (TPM) and gabapentin (GBP). METHODS: Forty healthy volunteers were randomized to a 12-week course of TPM, GBP, or placebo. Doses were gradually escalated over 10 weeks to a maximum of 400 mg/day of TPM or 3,600 mg/day of GBP or to the highest tolerated dose. Subjects were interviewed and examined biweekly. Cognitive testing was performed prior to initiating the drug and again 12 weeks later, at least 2 weeks after achieving plateau dosing. For each subject and cognitive measure, test-retest Z scores were calculated based on regression equations derived from 73 healthy volunteers. Group comparisons utilized the Wilcoxon test. RESULTS: There were significant TPM vs GBP and TPM vs placebo differences in test-retest Z scores for four of six target cognitive measures (Digit Symbol, Story Recall, Selective Reminding, Controlled Oral Word Association), always indicating worse retest performance for subjects receiving TPM. Overall, 12 of 24 cognitive measures were similarly affected. TPM effects were large, and several target measures averaged >2 SD of negative change. One measure was significantly affected by GBP. CONCLUSIONS: Topiramate (TPM) impaired cognitive test performance, whereas gabapentin had minimal effects. The effects of TPM were of sufficient magnitude potentially to affect daily and occupational function."

Effects of topiramate and gabapentin on cognitive abilities in healthy volunteers.