Combination Of Sodium Valproate Research Articles

DYKE DAVIDOFF MASSON SYNDROME-AN UNUSUAL CAUSE OF REFRACTORY SEIZURE: A RARE CASE REPORT

BACKGROUND: Dyke-Davidoff-Masson Syndrome (DDMS) is a rare neurological condition characterized by drug-resistance seizures, hemiparesis, mental retardation, facial asymmetry, and intellectual disabilities. On brain imaging, the disease is characterized by cerebral hemi atrophy with ipsilateral calvarial thickening and hyperpneumotisation of paranasal sinuses or mastoid air cells. INTRODUCTION: we describe a rare case of Dyke Davidoff Masson syndrome with an unusual cause of refractory seizure in an adolescent. Diagnosis: DDMS was diagnosed from its manifestations, biochemistry indexes, and imaging (computed tomography angiography, magnetic resonance venography, and so on). Interventions: Several drugs are used to treat the disease, including valproate, carbamazepine, topiramate, and levetiracetam. Outcomes: Under the medicine treatment of sodium valproate, levetiracetam and carbamazepine, the patient experienced generalized tonic clonic seizure seizures approximately once or twice per month that lasted 30 to 60seconds each without any complications observed during a follow-up period of. CONCLUSIONS: It was concluded early diagnosis and pharmacotherapy are the keys to preventing intellectual decline in DDMS patients. Moreover, the combination of sodium valproate, levetiracetam and carbamazepine could signicantly reduce the frequency and duration of seizures, despite not eliminating them completely24months

Comparison of Adjunctive Quetiapine Versus Adjunctive Haloperidol in Combination with Sodium Valproate for Treatment of Patients with Mania or Mixed Feature Bipolar I Disorder: A Randomized Double-Blind Clinical Trial Study

Background: Acute mania causes many problems for the patient and others. Therefore, it is very important to eliminate the symptoms quickly. Objectives: The present study made the individual comparison of the therapeutic effects of sodium valproate combined with quetiapine or haloperidol as an add-on among patients with bipolar I disorder experiencing an episode of mania or mixed feature admitted to a Psychiatric Center in Tehran. Methods: The present study was a double-blind clinical randomized trial conducted on 36 patients. All patients were investigated by the Young Mania Rating Scale (YMRS). The study lasted six weeks in total (after raising drug dosage to the maximum level). We prescribed sodium valproate 15 mg/kg plus quetiapine 500 mg daily in one group and sodium valproate 15 mg/kg plus haloperidol 10 mg daily in the other group. In addition, an equivalent dosage of quetiapine and haloperidol was prescribed. This study used different data analysis methods such as Paired t test, ANOVA, and chi-square test. Results: The YMRS scores did not show any statistically significant difference between quetiapine and haloperidol receiving groups (P > 0.05). Conclusions: This paper argued that a combination of sodium valproate with either quetiapine or haloperidol could be effective in the management of acute mania or mixed bipolar I disorder to reduce the severity and duration of symptoms, although there was no statistically significant difference between the efficacy of these two pharmacological therapies.

Patterns of cardiac ischemic changes among adult Sudanese epileptic patients attending Daoud Charity Clinic - Sudan January – May 2019

Introduction Epilepsy is one of the commonest neurologic disorder, with >85% of patients with epilepsy living in low and middle-income countries. Studies have shown that patients with epilepsy have a higher prevalence of structural cardiac disease than those without epilepsy. Seizure activity may not only induce arrhythmias but may also lead to structural cardiac changes. Objectives This study conducted to determine the patterns of cardiac ischemic changes among epileptic patients. Methodology A Community base study was conducted at Daoud Charity Clinic, and case series study design was used. A questionnaire, interviewer–administered, which included 13 items, was employed on a convenient sample consisting of 20 patients. Electrocardiography and echocardiography were used. Results Twenty patients were included with age between eighteen and fifty years, thirteen of them were female and seven were male. Twelve patients presented with tonic clonic, Four patients presented with focal to bilateral and cases of myoclonic, tonic, and focal without impair was observed. Twelve patients are taking sodium valproate, five patients are taking carbamazepine and three patients are taking combination of sodium valproate and carbamazepine. Two patients have ST- segment Abnormalities (St-segment depression and elevation). All patients have normal echocardiography. Conclusion There is a strong relationship between cardiac ischemia and epilepsy, St-segment abnormalities are the commonest finding.

The Therapeutic Effects of Low-Frequency Electrical Stimulations Adjunct to Sodium Valproate on Seizure and Behaviors.

Introduction:Consuming antidepressant medications induce several problems leading to the need for alternative agents for emotional disturbances. Antidepressant medications increase the seizure risk; thus, alternative treatments, like Antiepileptic Drugs (AED), might be useful for patients with epilepsy comorbid with a psychiatric disorder. The present study evaluated the behavioral effects of sodium valproate, a none effective dose in seizure treatment [100 mg/kg; Intraperitoneal (IP)] along with the application of Low-Frequency Stimulations (LFS) during CA1 hippocampal kindling.Methods:In total, 42 male rats were randomly divided into 6 groups, including control group with intact animals handled daily (I); sham group which was subjected to the surgical process, but received no real stimulation (II); saline-kindled Kindled group (S.kindled) which were stimulated daily with the following protocol: 3 strain of 50Hz monophasic pulses of 1ms duration applied 12 times a day with the threshold intensity at intervals of 10 minutes where saline was administrated 15 min before kindling stimulations (III); saline-kindled-LFS group (K4LFS) in which saline was injected 15 min before kindling stimulations and LFS was applied daily after the termination of kindling stimulation (IV); drug-kindle group (Drug100.kindled) that underwent rapid kindling procedure daily where sodium valproate (100 mg/kg) was administrated 15 min before kindling stimulations(V), and drug-kindled-LFS (Drug100.kindled.4LFS) group in which drug and LFS were administrated respectively before and after kindling stimulations (VI). The behavioral tests were assessed using elevated plus maze, open field, and forced swim tests.Results:The combination of sodium valproate (100 mg/kg) and LFS significantly decreased cumulative seizure severity compared with the kindle group. Thus, it provided a strong seizure suppressing effect. Additionally, sodium valproate and LFS increased the percentage of Open Arms (OAs) entries and the OAs exploration; they also decreased jumping from elevated plus maze test and rearing in open field test. Furthermore, there was no significant change in the OAs entries and OAs exploration percentages, jumping from apparatus, and rearing in open field in Drug100. Kindled, K4LFS, and Drug100.kindled.LFS groups, compared with the sham group. There was no significant difference in the latency to first immobility and the duration of immobility in K4LFS groups compared with the S. kindled group. In the drug-kindled group, the latency to first immobility significantly increased, and the duration of immobility decreased, compared with the S. kindled group. Besides, the latency to first immobility significantly increased, and the duration of immobility decreased in drug-kindled-LFS, compared to S. kindled group; however, the latency to first immobility was not significantly changed, compared to drug-kindled groups.Conclusion:Sodium valproate and LFS can modulate the function of the brain regions involved in emotional processing in epilepsy, as well as anxiety- and depressive-like behaviors. Such a combination could also decrease emotional disturbances induced by the kindling process.

Evaluation of analgesic activity of sodium valproate and ethanolic extract of Vitex negundo in experimental analgesic models in wistar rats

Background: NSAIDs and opioids are commonly prescribed medications to relieve pain of multiple aetiologies with no effect on the level of consciousness of the patient. They interfere with the mode of transmission of the pain message. A widely prescribed antiepileptic drug, sodium valproate has been used in various non-epileptic conditions like migraine prophylaxis and in the treatment of bipolar disorder because of the multiple mechanisms by which it acts. Vitex negundo has been investigated for antipyretic, analgesic, anti-inflammatory, anticonvulsant, hepatoprotective and bronchial relaxant. Very few studies have been done to evaluate its analgesic activity and no study was done on analgesic activity with the combination of modern drug. The more important point to be noted is that Vitex negundo is a natural product and therefore unlikely to cause adverse effects when compared to the traditional drugs used to treat pain. The aim of the present study was to evaluate of analgesic activity of sodium valproate and docosahexaenoic in experimental analgesic models in wistar rats.Methods: For analgesic activity, a total of 36 adult Wistar albino rats were taken and divided into six groups of six rats each. Group I was control (distil water 1ml/kg), Group II received intraperitoneal injection of diclofenac sodium (10mg/kg), Group III, IV were injected intraperitoneal sodium valproate 200, 400mg/kg with distil water respectively and Group V, VI were given sodium valproate 200, 400mg/kg (intraperitoneal) plus EEVN 400mg/kg (orally) respectively. Analgesic activity was assessed using hot plate, tail flick and acetic acid writhing models.Results: Present study revealed that sodium valproate at higher doses (400mg/kg) used either alone along with EEVN (400mg/kg) showed statistically significant analgesic activity in comparison to control in various experimental models for assessing pain.Conclusions: Combination of sodium valproate along with EEVN has shown promising analgesic activity.

Modulatory effects of some natural products on hepatotoxicity induced by combination of sodium valproate and paracetamol in rats.

Possible hepatoprotective effect of Curcuma longa and/or Nigella sativa against hepatotoxicity induced by coadministration of sodium valproate (SV) and paracetamol was studied. Rats were divided into 10 groups, control groups 1, 2, 3, and 4 received vehicles, C. longa (200mg/kg, p.o.), N. sativa (250mg/kg, p.o.), or both herbs for 21days, respectively. Toxicity groups 5, 6, and 7 received SV (300mg/kg, i.p.), paracetamol (1000mg/kg, p.o.) for the last 4days or both for 21days, respectively. Protection groups 8, 9, and 10 received C. longa, N. sativa, or both, respectively, 1h before the administration of both the drugs for 21days. SV and/or paracetamol significantly increased aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), total bilirubin, relative liver/body weight ratio, malondialdehyde (MDA), tumor necrosis factor alpha (TNF-α), and caspase-3 (Casp-3) while significantly decreased albumin, total protein, glutathione (GSH) reduced, GSH peroxidase, and superoxide dismutase (SOD). Preadministration of C. longa and/or N. sativa caused protective effect against the hepatotoxicity induced by both drugs.

Comparison of efficacy between risperidone and aripiprazole in combination with sodium valproate in patients with acute manic or mixed episodes

Today, despite of the improvement in the psychological therapeutic approach, mania still remains as a challenging problem for health system. The aim of this study is comparison efficacy of risperidone and aripiprazole in combination with sodium valproate in bipolar patients with acute manic or mixed episodes who hospitalized in Razi psychiatric hospital in Tehran. This study was conducted as a double blind randomized clinical trial in two groups of bipolar disorder patients with manic or mixed episodes (18–65 age). Patients randomly set in two groups who received valproate with aripiprazole or risperidone. Clinical response was assessed with young mania rating scale (YMRS) and weight gain at 3 and 6 weeks. Data was analyzed with Chi2 test, paired t-test and analysis of covariance and repeated measurement. Evaluation of treatment response after 3 and 6 weeks (50% reduction in Young's scale) in both groups did not show any significant difference between the two therapeutic combinations. The combination of sodium valproate and risperidone showed higher weight gain in comparison with the combination of valproate and aripiprazole at the end of week 6 (P < 0.001). The mentioned combination in bipolar I disorder with manic or mixed episode has similar therapeutic effect, so that both of them are effective and usable. There was no difference in their efficacy, and both treatments can be used. Due to the less weight gain, the combination of valproate and aripiprazole in patients who prone to weight gain, this approach is recommended as more safe and effective therapy.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Investigation of the effects of magnesium orotate in a model of primary generalized seizures

Objective : to investigate the anticonvulsant and neuroprotective effects of magnesium orotate in a rat thiosemicarbazide model of seizures in rats. Material and methods . The investigation was conducted in 112 male albino rats weighing 200 g, in which severe clonic-tonic seizures weresimulated by the convulsant thiosemicarbazide. The anticonvulsant effects against of thiosemicarbazide-induced seizures were evaluated in the following drugs: gabapentin; a combination of gabapentin + magnesium orotate; sodium valproate; a combination of sodium valproate + magnesium orotate; and magnesium orotate. The neurological status, characteristics of seizures, survival rates, body weight, and plasma and red blood cell magnesium concentrations were compared. After completing the animal experiment, the animals were euthanized and the histological characteristics of their brains and nerves were analyzed. Results. Magnesium orotate was ascertained to reduce the severity and duration of thiosemicarbazide-induced seizures, to increase animal survival rates, and to potentiate the anticonvulsant action of gabapentin and sodium valproate. The neurohistological findings showed that the used model of seizures led to ischemic brain damage. Conclusion . It has been concluded that magnesium orotate minimized the level of ischemic damage to nerve cells and contributed to restoration of the morphology of brain tissues after thiosemicarbazide administration.

Nephrotoxicity of sodium valproate and protective role of L-cysteine in rats at biochemical and histological levels.

This study investigated whether the combination of sodium valproate (SV) with L-cysteine (LC) can decrease the SV toxicity of kidneys. SV caused alternation in oxidative/antioxidant balance. Biochemical estimations included the determination of oxidative stress markers like thiobarbituric acid-reactive substances in kidney tissue, and enzymatic antioxidant activities such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase as well as total antioxidant capacity were evaluated in renal tissues. Creatinine and uric acid levels in the serum were also determined to assess kidney function. Pathological examination of the kidney was also performed. Increasing the levels of lipid peroxidation and decreasing the enzymatic activity (SOD, CAT, and GPx) as well as total antioxidant capacity of rats was shown with different doses of SV. Impairment in renal function tests suggests a decreased glomerular filtration rate, as serum creatinine was elevated. Histopathological changes of kidney tissue treated with SV reveal the proximal and the distal convoluted tubules that show hydropic changes (small white vacuoles within the cytoplasm and the glomeruli show hypercellularity). The concurrent administration of LC with SV significantly had beneficial effects on the kidney and all the above parameters have been improved.

EFFECT OF SODIUM VALPROATE AND DOCOSAHEXAENOIC ACID ON INFLAMMATION IN RATS

ABSTRACTObjective: To evaluate the anti-inflammatory activity of sodium valproate and docosahexaenoic acid (DHA) supplementation using variousexperimental models in albino Wistar rats.Method: A total of 48 adult Wistar albino male rats were divided into 8 groups of 6 rats each. Group I was control (distilled water 1 ml/kg), Group IIreceived intraperitoneal (i.p.) injection of indomethacin (10 mg/kg), Groups III-V were injected (i.p.) with sodium valproate 100, 200, and 400 mg/kgwater, and Groups VI-VIII were given sodium valproate 100, 200, and 400 mg/kg plus DHA 300 mg/kg (i.p.), respectively. Anti-inflammatory activitywas assessed using carrageenan induced paw edema and the cotton pellet granuloma models.Results: We found that higher doses of sodium valproate (400 mg/kg) used either alone or with a combination of DHA (300 mg/kg) showed asignificant anti-inflammatory activity when compared to control in both the models of inflammation.Conclusion: Combination of sodium valproate along DHA has shown promising anti-inflammatory activity.Keywords: Anti-inflammatory drugs, Sodium valproate, Rat model.

Evaluation of chitosan–anionic polymers based tablets for extended-release of highly water-soluble drugs

The objective of this study is to develop chitosan–anionic polymers based extended-release tablets and test the feasibility of using this system for the sustained release of highly water-soluble drugs with high drug loading. Here, the combination of sodium valproate (VPS) and valproic acid (VPA) were chosen as the model drugs. Anionic polymers studied include xanthan gum (XG), carrageenan (CG), sodium carboxymethyl cellulose (CMC-Na) and sodium alginate (SA). The tablets were prepared by wet granulation method. In vitro drug release was carried out under simulated gastrointestinal condition. Drug release mechanism was studied. Compared with single polymers, chitosan–anionic polymers based system caused a further slowdown of drug release rate. Among them, CS–xanthan gum matrix system exhibited the best extended-release behavior and could extend drug release for up to 24 h. Differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FTIR) studies demonstrated that polyelectrolyte complexes (PECs) were formed on the tablet surface, which played an important role on retarding erosion and swelling of the matrix in the later stage. In conclusion, this study demonstrated that it is possible to develop highly water-soluble drugs loaded extended-release tablets using chitosan–anionic polymers based system.

Familial hemiplegic migraine treated by sodium valproate and lamotrigine

Familial hemiplegic migraine (FHM) is a rare monogenic subtype of migraine with aura that includes motor auras. Prophylactic treatment of FHM often has marginal effects and involves a trial-and-error strategy based on therapeutic guidelines for non-hemiplegic migraine and on case reports in FHM. We assessed the response to prophylactic medication in an FHM family and sequenced the FHM2 ATP1A2 gene in all available relatives. A novel p.Met731Val ATP1A2 mutation was identified. Attack frequency was reduced significantly with sodium valproate monotherapy (n = 1) and attacks ceased completely with a combination of sodium valproate and lamotrigine (n = 2). We report dramatic prophylactic effects of sodium valproate and lamotrigine in an FHM2 family, making these drugs worth considering in the treatment of other FHM patients.

Study of potential drug-drug interactions between benzodiazepines and four commonly used antiepileptic drugs in mice

Background: Benzodiazepines (BZD) is one of the commonly used drug groups for certain neurological diseases. As sometimes, the anti-epileptic drugs (AEDs) may be used concomitantly with BZD there is a potential for drug-drug interactions. Study aimed to study potential drug-drug interactions between four commonly used AEDs (phenytoin, carbamazepine (CBZ), phenobarbitone, sodium valproate) and BZD (diazepam, clonazepam) in mice using maximal electroshock seizure (MES) method and pentylenetetrazole (PTZ) method. Methods: Adult male albino mice were divided into four different groups of six animals each and anti-epileptic activity was assessed using MES method and PTZ method. Group I acted as a control, Group II received any one of the four AEDs (phenytoin, CBZ, phenobarbitone or sodium valproate) in sub-effective doses, Group III received diazepam or clonazepam alone, Group IV received a combination of diazepam or clonazepam with any one of the AEDs. Results: In MES method, the groups receiving combination of diazepam with phenytoin and CBZ showed significant protection compared to the control group (p<0.01 and p<0.02), respectively. However, diazepam in combination with sodium valproate and phenobarbitone did not show any significant protection compared to the control group and individual antiepileptic group. All the four antiepileptic showed significant protection against MES seizure in combination with clonazepam when compared to control group. In PTZ method, combination of sodium valproate with clonazepam showed significant protection compared to control group (p<0.02). However, this was not observed with diazepam-valproate combination. Conclusion: Clonazepam potentiates the action of all the four anti-epileptics while diazepam potentiates only phenytoin and CBZ against MES seizures. Clonazepam but not diazepam potentiates the action of sodium valproate against PTZ seizures.

Interactions between carvedilol and sodium valproate along with neurobehavioural co-morbidities in various epilepsy models

ObjectiveThis study evaluated the effect of carvedilol (CRV) commonly used antihypertensive drugs on the antiepileptic drug sodium valproate (SVP) along with neurobehavioural co-morbidities in various models of epilepsy. MethodsFor this purpose, we used the Increasing Current Electroshock Seizure (ICES) test and Pentylenetetrazole (PTZ) test in mice. Additionally, adverse effects of combined treatment with the drugs in the Spontaneous Alternation Behavior (SAB) and rotarod were assessed. The levels of TBARS and the Reduced Glutathione (GSH) were determined in brains of mice for investigation of the oxidative stress. All drugs were administered orally. ResultsSVP (50 & 100 mg/kg) and CRV (1.25, 2.5 & 5.0 mg/kg) alone as well as in combination significantly enhanced the seizure threshold in the ICES test and PTZ test. CRV significantly increase the percentage alternation scores as compared to control group whereas combination of SVP with CRV did not affect the percentage alternation scores. In the present study, CRV and SVP alone as well as in combinations had no significant effect on motor parameters, at any of the given doses. CRV and SVP alone as well as in combination shown to inhibit the lipid peroxidation and increase in the level of GSH in brain tissue in a dose dependent manner which showed that it reduces the oxidative stress. ConclusionThe current study suggests that CRV potentiate the anticonvulsant activity of VPA. Therefore, the observed interaction could be pharmacodynamics in nature.

A combined pretreatment of 1,25-dihydroxyvitamin D3 and sodium valproate enhances the damaging effect of ionizing radiation on prostate cancer cells

Radiotherapy is one of the curative treatment options for prostate cancer (PCa). However, effective doses of ionizing radiation (IR) have a high risk of side effects. To increase sensitivity of PCa to IR we pretreated human androgen-refractory DU145 PCa cells with a combination of sodium valproate (VPA), a well-tolerated drug with histone deacetylases inhibiting activity, and 1,25-dihydroxyvitamin D3, 1,25(OH)2D3, the active metabolite of vitamin D, a well known anticancer agent. The results show that irradiation (4 Gy) of DU145 PCa cells pretreated with a combination of 1 mM VPA and 100 nM 1,25(OH)2D3 efficiently suppressed (87.9%) PCa cell proliferation. IR after combined pretreatment resulted in increased DNA double-strand breaks expressed as levels of phosphorylated histone H2A.X, compared with non-treated cells the increase was 58.1% in pretreated cells and 11.8% in non-pretreated cells ( p < 0.002). Combined pretreatment enhanced IR-induced activation of DNA damage checkpoint kinase Chk2, 39.0% in pretreated cells compared to 23.8% in non-pretreated cells ( p < 0.05). These molecular changes led to DNA replication blockade, S-phase cell-cycle arrest and enhanced apoptosis. Cumulatively, the results indicate that combined pretreatment with VPA and 1,25(OH)2D3 followed by IR is a highly effective treatment for human PCa cells. This observation may have important implications for reducing doses of radiation administered to cancer patients thus limiting the severity of side effects.

Modulation of pentylenetetrazole‐induced seizures and oxidative stress parameters by sodium valproate in the absence and presence of N‐acetylcysteine

In view of a role of oxidative stress in epilepsy and the evidence for the involvement of peroxidative injury in sodium valproate (SVP)-induced adverse effects on liver and kidneys, we investigated whether the combination of SVP with N-acetylcysteine (NAC), an antioxidant, may help us to achieve maximal efficacy in terms of seizure control, with minimal toxicity on liver and kidneys. Pentylenetetrazole (PTZ)-induced seizures were used to evaluate the anticonvulsant effect of drugs. Biochemical estimations included the determination of oxidative stress markers like thiobarbituric acid-reactive substances in brain tissue and glutathione (GSH) levels in liver and kidney tissues. Aspartate aminotransferase and alanine aminotransferase concentrations in the serum were also determined to assess liver function. In our study, NAC exhibited a nondose-dependent anticonvulsant effect. The concurrent administration of NAC with SVP significantly prolonged the latency to jerks, myoclonus and clonic generalized seizures. No significant oxidative stress was evident in brain tissue following PTZ-induced seizures, though an elevation of serum transaminase enzymes was seen. SVP at the dose studied did not produce any significant oxidative stress on the liver and kidneys, while treatment with NAC elevated liver and kidney GSH levels. The concurrent administration of NAC with SVP had beneficial effects on liver and kidney cells.

The Histone Deacetylase Inhibitor Sodium Valproate Has In Vitro Anti-Neoplastic Activity Against Primary Multiple Myeloma Cells and Cell Lines Both Alone and in Combination with Velcade.

There is growing evidence that histone deacetylase inhibitors (HDAC-I) may have benefit in the treatment of multiple myeloma (MM). We assessed the in vitro responses of the MM cell lines H929, JJN3, KMS11 and U266 to the HDAC-Is trichostatin A (TSA), suberoylanilide hydroxamic acid (SAHA) and sodium valproate (SV). All three HDAC-Is induced dose dependent cell killing and the ranked sensitivity of the lines was remarkably constant with U266 cells being most resistant to all three inhibitors. Real time RT-PCR based analyses of the HDAC expression profiles, identified that the greater resistence of U266 cells was associated with 5–10 fold increased expression of a single HDAC from the sirtuin family of deacetylases (SIRT5). Each HDAC-I displayed different potencies against the cell lines; TSA killed in the range 0.1–1μM, SAHA in the range 1–10μM and SV at the higher doses of 1–10mM. Despite being less potent, the doses of SV are commensurate with those that can be achieved in vivo. Furthermore, we have identified synergy/cooperation between suboptimal SV concentrations and the proteasome inhibitor Velcade (Bortezomib). MTT assays using JJN3 cells, demonstrated that 1mM SV had little effect reducing survival to 89% whereas 0.6 nM velcade reduced cell survival to 42±5.5%. Killing by velcade was not significantly enhanced by the additional presence of 1μM dexamethasone (Dex)(36±3.4%). However, the combination of SV, Dex and Velcade resulted in near total cell killing (4.7±2.6% survival). Collectively, these observations suggested that SV may have value in MM therapy. However, we wished to also investigate the potency of SV against primary MM cells. We have developed an in vitro culture system in which primary MM plasma cells survive for up to 30 days. In this culture system we have observed efficient and selective killing of MM cells by 1mM SV that has been comparable or indeed greater than that observed in response to 1μM SAHA. Thus it appears that primary MM cells are more SV sensitive than MM cell lines. Together our findings indicate that SV may have value in MM therapy and in particular when combined with proteasome inhibitors. Our data also indicate that SIRT5 overexpression may be a resistance factor against such therapies.

Gabapentin-Associated Aggression

Back to table of contents Previous article Next article LetterFull AccessGabapentin-Associated AggressionNarsimha R. Pinninti, M.D., , and Deepak S. Mahajan, M.D., Narsimha R. PinnintiSearch for more papers by this author, M.D., Department of Psychiatry, SOM-UMDNJ, Cherry Hill, NJ, and Deepak S. MahajanSearch for more papers by this author, M.D., Philadelphia, PAPublished Online:1 Aug 2001AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail SIR: Gabapentin is an effective adjunctive mood stabilizer.1 There are case reports of aggression and hyperactivity when gabapentin was added to existing antiepileptic medication2 or used as a monotherapy in children.3 In adults, hostility, but not aggressive behavior, is reported to occur in at least 1% of patients treated with gabapentin.4 We report two cases where introduction of gabapentin was associated with aggressive behavior.Case ReportsCase 1. A 38-year-old man was admitted for the third time to our facility with a diagnosis of bipolar disorder, manic phase with psychotic symptoms. There was no history of rapid cycling, comorbid substance abuse, or physical aggression. His symptoms were partially responsive to a combination of lithium carbonate 1,650 mg/day (level of 0.7 mEq/l), olanzapine 25 mg/day, and lorazepam 2 mg bid. Gabapentin was started in a dose of 300 mg tid and increased to 1,200 mg/day by day 3. By day 4, the patient became very irritable and physically aggressive. He attacked a nurse, and mechanical restraints were used to control his behavior. He did not receive any additional medication at this time. The patient later recognized this behavior as out of character for him. Gabapentin was stopped while all other medications were continued. Within a day, his irritability decreased and aggressive behavior stopped completely. No further incidents of aggression were noted throughout the rest of his hospital stay.Case 2. A 51-year-old man with a diagnosis of bipolar disorder was admitted for the fourth time to our facility in a manic phase with mixed affective features. He had no history of psychotic symptoms, substance abuse, or aggression. On a combination of sodium valproate 2 g/day and risperidone 4 mg/day (to which the patient had responded well on previous admission) he became very withdrawn, spending 12 hours a day in bed, but denied depressive symptoms. When a reduction in sodium valproate to 1 g did not improve his condition, a decision was made to switch mood stabilizers. Gabapentin was started in a dose of 300 mg bid, and sodium valproate was stopped. Within 48 hours, the patient developed new symptoms of hostility, verbal aggression, and command auditory hallucinations and destroyed property by breaking the commode in his room. The patient clearly attributed these new symptoms to gabapentin. Gabapentin was stopped and sodium valproate reinstated in a dose of 1g per day. Within 48 hours, hostility, aggressive behavior, and hallucinations stopped. No further aggressive behavior was noted throughout his hospital stay.CommentAggression in the above two cases could be an aspect of mania, or it could be gabapentin-related. The absence of prior aggression, the temporal relation to instituting gabapentin, the cessation of aggression soon after stopping gabapentin, and the ego-dystonic nature of the aggressive behavior indicate an association between gabapentin and aggression. To our knowledge, there are no published case reports of aggression with gabapentin in adult patients. More than 100 cases of hostility and aggression have been reported to the manufacturer in the past 5 years (personal communication, Parke-Davis, 2000). With increasing use of gabapentin in psychiatry, this possible adverse effect should be kept in mind.References1 Ferrier IN: Lamotrigine and gabapentin: alternative in treatment of bipolar disorder. Neuropsychobiology 1998; 38:192-197Crossref, Medline, Google Scholar2 Wolf SM, Shinnar S, Kang H, et al: Gabapentin toxicity in children manifesting as behavioral changes. Epilepsia 1996: 36:1203-1205Google Scholar3 Tallian KB, Nahata MC, Lo W, et al: Gabapentin-associated aggressive behavior in pediatric patients with seizures. Epilepsia 1996; 37(suppl):501-502Google Scholar4 Neurontin (gabapentin). Physician's Desk Reference, 55th edition. Montvale, NJ, Medical Economics Co, 2001, p 2460Google Scholar FiguresReferencesCited byDetailsCited byEffect of gabapentin on sleep-deprivation-induced disruption of prepulse inhibition27 June 2020 | Psychopharmacology, Vol. 63BMJThe Psychopharmacology of Aggressive BehaviorJournal of Clinical Psychopharmacology, Vol. 32, No. 2The Consultant Pharmacist, Vol. 22, No. 12Gabapentin-Induced Paradoxical Exacerbation of Psychosis in a Patient with Schizophrenia1 December 2002 | The Canadian Journal of Psychiatry, Vol. 47, No. 10 Volume 13Issue 3 August 2001Pages 424-424 Metrics PDF download History Published online 1 August 2001 Published in print 1 August 2001

Antiepileptic effects of a combination of sodium valproate and the calcium antagonist ryodipine on a model of generalized metrazol-induced epileptic activity

Antiepileptic effects of a combination of sodium valproate and the calcium antagonist ryodipine on a model of generalized metrazol-induced epileptic activity

Spinal Myoclonus

We describe a 37-year-old man with spinal segmental myoclonus characterized by symmetric, rhythmic contractions of the abdomen with a frequency ranging between 100 and 150/min. The combination of sodium valproate and L-5-hydroxytryptophan was useful to control the myoclonus. We comment on the possible role of the serotonergic system in this syndrome.