Topiramate in Opiate Withdrawal-Comparison with Clonidine and with Carbamazepine/Mianserin

University Department of Adult Psychiatry, Lausanne, Switzerland.
Substance Abuse (Impact Factor: 2.1). 12/2004; 25(4):27-33. DOI: 10.1300/J465v25n04_04
Source: PubMed


There are some rationales for developing anticonvulsants for the treatment of substance abuse. The blockade of the AMPA/kainate subtype of glutamate receptor by topiramate may be of particular interest, as preclinical studies of withdrawal from opioids suggest that whilst AMPA-receptor antagonists may not be able to prevent tolerance or dependence from developing, they may ameliorate both physical and emotional consequences of withdrawal.
Ten consecutively admitted patients treated with topiramate were compared in a retrospective naturalistic drug utilization observation study with 10 consecutively admitted patients treated with clonidine and with 10 consecutively admitted patients treated with a carbamazepine/ mianserin combination.
In 9 cases of the clonidine group and in 7 carbamazepine/mianserin treated patients the dose had been reduced, whereas this occurred in only 2 topiramate treated patients (p < 0.01). Patients in the topiramate group received less p.r.n. myorelaxant medication than the two other groups, and there was a significant difference between the three groups with regard to p.r.n. analgesics (p < 0.05), topiramate and clonidine treated patients receiving fewer analgesics than the carbamazepine/mianserin group.
Compared to clonidine and carbamazepine/mianserin, a detoxification scheme using high initial and then decreasing doses of topiramate appeared to be appropriate for most patients and as associated with less analgesic and myorelaxant comedication, indicating a more promising efficacy at the used doses.

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    • "Effects of lamotrigine on morphine withdrawal syndrome are contro-versial(1819). Also anticonvulsants have repeatedly been proposed as a treatment of alcohol and cocaine withdrawal(20–23), and some data exist on ameliorating both physical and emotional consequences of opioid withdrawal(2425). Therefore anticonvulsants may be promising alternatives to clonidine or opiate tapering as a treatment for opiate withdrawal. "
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    ABSTRACT: This study was designed to assess the effect of five common anticonvulsant drugs on naloxone-precipitated withdrawal syndrome in morphine-dependent mice. Male mice (25-35 g) were made dependent by increasing doses of morphine (30-90 mg/kg). At least three doses of phenytoin, carbamazepine, sodium valproate, lamotrigine and topiramate were injected i.p. to morphine-dependent mice 45 min prior to induction of withdrawal syndrome by naloxone (5 mg/kg, i.p.). Control animals received vehicle. Number of jumpings was counted and ptosis, tremor, piloerection and diarrhea were checked in a 30 min period started just after naloxone injection. Results showed that lamotrigine, phenytoin and sodium valproate were ineffective in suppression of withdrawal syndrome while carbamazepine produced a dose-dependent reduction of jumpings. Topiramate at the maxium applied dose (100 mg/kg) significantly reduced number of naloxone-elicited jumpings. It seems that carbamazepine by inhibition of N-Methyl-D-Aspartate (NMDA) receptors and topiramate by inhibiting kainite-activated (AMPA) receptor antagonists suppress morphine withdrawal syndrome but further studies are needed to have a definite conclusion.
    Research in pharmaceutical sciences 03/2011; 6(1):57-62.
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    • "Diverse studies and case reports have recently raised the interest of topiramate in the treatment of addictive disorders such as alcohol dependence [7,8], opiates [9] and benzodiazepines withdrawal [10], smoking cessation (Khazaal et al in press), but also in other disorders characterized by compulsive behavior like binge eating disorder [11], bulimia nervosa [12], obesity [13], Tourette's syndrome [14], flash-backs and nightmares in PTSD [15], and self-mutilation behavior [16]. "
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    ABSTRACT: Among the multiple mechanisms of action of topiramate, AMPA/kainate antagonism may be particularly interesting for the treatment of disorders characterized by conditioned cognitive and behavioral cue reactivity. We report the case of a patient consulting primarily for obesity and cue triggered snacking, who responded well on topiramate at doses up to 50 mg. Coincidentally he reported on an improvement of compulsive nonparaphilic sexual behaviors (consumption of prostitution), which was also strongly triggered by environmental cues. Both addictive behaviors (snacking and consumption of prostitution) reoccurred after discontinuation of topiramate and again responded reintroduction of the drug. The present case report of topiramate's effect on comorbid obesity and nonparaphilic addiction could be interpreted as a further indication that topiramate acts on the common pathway underlying conditioned behaviors and seems to be a treatment of behavioral disorders associated with environmental cues.
    BMC Psychiatry 02/2006; 6:22. DOI:10.1186/1471-244X-6-22 · 2.21 Impact Factor
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    ABSTRACT: Due to its AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid)/kainate antagonism, topiramate would be particularly interesting in addiction treatment. Flexible-dose topiramate was prescribed to 13 smokers (10 smokers who wanted to stop smoking, and three who received topiramate for other reasons). Six out of 13 smokers were abstinent at 2 months and two more subjects had reduced their cigarette consumption by >50%. With one exception, temporary reduction of the number of smoked cigarettes preceded definitive abstinence at month 2. Three more subjects who achieved a momentary reduction had, however, to interrupt the treatment due to intolerable side-effects. Controlled trials are needed to confirm these preliminary observations.
    Psychiatry and Clinical Neurosciences 06/2006; 60(3):384-8. DOI:10.1111/j.1440-1819.2006.01518.x · 1.63 Impact Factor
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