Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0040822 (tremor)
 18,428 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Antiepileptic drugs (AEDs) are used extensively to treat multiple non-epilepsy disorders, both in neurology and psychiatry. This article provides a review of the clinical efficacy of AEDs in non-epilepsy disorders based on recently published preclinical and clinical studies, and attempts to relate this efficacy to the mechanism of action of AEDs and pathophysiological processes associated with the disorders. Some newer indications for AEDs have been established, while others are under investigation. The disorders where AEDs have been demonstrated to be of clinical importance include neurological disorders, such as essential tremor, neuropathic pain and migraine, and psychiatric disorders, including anxiety, schizophrenia and bipolar disorder. Many of the AEDs have various targets of action in the synapse and have several proposed relevant mechanisms of action in epilepsy and in other disorders. Pathophysiological processes disturb neuronal excitability by modulating ion channels, receptors and intracellular signalling pathways, and these are targets for the pharmacological action of various AEDs. Attention is focused on the glutamatergic and GABAergic synapses. In psychiatric conditions such as schizophrenia and bipolar disorder, AEDs such as valproate, carbamazepine and lamotrigine appear to have clear roles based on their effect on intracellular pathways. On the other hand, some AEDs, e.g. topiramate, have efficacy for nonpsychiatric disorders including migraine, possibly by enhancing GABAergic and reducing glutamatergic neurotransmission. AEDs that seem to enhance GABAergic neurotransmission, e.g. tiagabine, valproate, gabapentin and possibly levetiracetam, may have a role in treating neurological disorders such as essential tremor, or anxiety disorders. AEDs with effects on voltage-gated sodium or calcium channels may be advantageous in treating neuropathic pain, e.g. gabapentin, pregabalin, carbamazepine, oxcarbazepine, lamotrigine and valproate. Co-morbid conditions associated with epilepsy, such as mood disorders and migraine, may often respond to treatment with AEDs. Other possible disorders where AEDs may be of clinical importance include cancer, HIV infection, drug and alcohol abuse, and also in neuroprotection. A future challenge is to evaluate the second-generation AEDs in non-epilepsy disorders and to design clinical trials to study their effects in such disorders in paediatric patients. Differentiation between the main mechanisms of action of the AEDs needs more consideration in drug selection for tailored treatment of the various non-epilepsy disorders.
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PMID:Antiepileptic drugs in non-epilepsy disorders: relations between mechanisms of action and clinical efficacy. 1807 13

Two patients with bipolar disorder had been treated for years with lithium without any complications but began to develop symptoms of rigidity and an altered gait, namely symptoms compatible with a diagnosis of Parkinsonism with an action tremor. In both patients lithium levels were within the therapeutic range. Medication-induced Parkinsonism occurs frequently in patients using antipsychotic medication, but is a rare complication in patients receiving long term treatment with lithium. The lithium dosage was reduced gradually and within a few months all neurological symptoms subsided completely.
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PMID:[Parkinsonism during lithium use]. 1919 54

Valproate (2-propylpentanoate) is available as valproic acid, sodium valproate and semisodium valproate. It has actions on dopamine, GABA and glutamate neurotransmission and intracellular signaling. Its main psychiatric use is to treat bipolar disorder. It has been used in other psychiatric disorders, including schizophrenia and borderline personality disorder, but data are insufficient to recommend this. In acute mania, valproate monotherapy has similar efficacy to antipsychotic drugs and lithium whereas the combination of valproate and an antipsychotic is more effective than either drug alone. In maintenance treatment of bipolar disorder, valproate monotherapy has comparable efficacy to olanzapine although placebo-controlled evidence is limited. Maintenance treatment with valproate and quetiapine or olanzapine is more efficacious than valproate alone when an acute episode responds to the combination. Common adverse effects of valproate include weight gain, gastrointestinal symptoms, sedation, tremor and mild elevation of hepatic enzymes. Serious hepatic toxicity is rare in adults. Many adverse effects are dose related and resolve with dose reduction. Valproate is teratogenic and specifically associated with neural tube defect. Preliminary evidence has linked in utero exposure to decreased verbal intelligence in the offspring. These effects, plus a probable increased risk of polycystic ovary syndrome, limit valproate's use in women of childbearing potential.
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PMID:A review of valproate in psychiatric practice. 1940 30

Divalproex (DVP) delayed release and DVP extended release (DVP ER) are approved by the Food and Drug Administration for bipolar disorder, epilepsy, and migraine prophylaxis. Divalproex ER is given once daily, improving compliance and reducing adverse events. Overnight switch to DVP ER is advised in the package insert but could produce more adverse events in this susceptible population. In this pilot study, we compared tolerability of overnight versus gradual switching to DVP ER in 16 adults with intellectual and developmental disabilities receiving DVP, in 9 for epilepsy and in all 16 for comorbid bipolar disorder. The study design was open with parallel groups. Sixteen subjects with intellectual and developmental disabilities were randomized to overnight or gradual conversion for 4 to 6 days. A blinded rater completed the Multidimensional Observation Scale for Elderly Subjects on days +1, +4, and +8 after the switch began. We found no major differences between the 2 groups at each time point. Neither group of subjects, except for 1 subject in the overnight group, manifested sedation, seizures, worsening of tremor, or gastrointestinal adverse events. One subject in the overnight group manifested acute diarrhea and vomiting, followed by a very brief tonic leg seizure 6 days later. Larger studies are warranted.
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PMID:Overnight versus progressive conversion of multiple daily-dose divalproex to once-daily divalproex extended release: which strategy is better tolerated by adults with intellectual disabilities? 1974 51

One hundred and twenty-five patients (49 men and 76 women, mean age 38,0+/-12,5 years) were randomized in two groups. One group (64 patients) was treated with valproate sodium and another group (61 patients) received lithium carbonate. Monotherapy was administered with the mean dose of valproate 20 mg/kg/day (serum valproate concentration between 70 and 125 ?g/ml) and the mean dose of lithium 800 mg/day (between 600 and 900 mg/day; serum lithium concentration 0,8-1,2 mmol/L) during 12 weeks. Clinical effectiveness was assessed using YMRS, CGI-BP and MADRS at 0, 5th, 10th, 21st , 84th days of treatment. The number of responders (50% reduction in YMRS scores) was 51,7% (30 patients) in lithium group and 56,7% (34 patients) in valproate group by the 21st day (p=0,59).The mean reduction in YMRS scores was 11,6 in patients treated with lithium and 12,3 in patients treated with valproate. By the 84th day (LOCF), the number of responders reached 85% (51 patients) in lithium group and 90,3% (56 patients) in valproate group (p=0,37). The mean reduction in YMRS scores was 19,4 in patients treated with lithium and 19,6 in patients treated with valproate. The average reduction in MADRS scores was -1,4 (p=0,08) and -2,2 (p=0,001) in lithium group; -1,6 (p=0,002) and -1,4 (p=0,019) in valproate group on the 21st and 84th days. Adverse effects were observed in 8 (13,1%) patients who received lithium and 3 patients (4,7%) who received valproate (p=0,12). The most common of them were tremor, nausea, dry mouth. There were no clinically significant abnormalities in laboratory values, vital functions and EEG. In conclusion, the results demonstrated equal therapeutic efficacy, tolerability and safety of valproate and lithium in the treatment of manic episodes in patients with bipolar disorder.
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PMID:[Open randomized comparative twelve-week study of lithium and valproate in manic episode]. 2003 54

Practical strategies are available for primary care physicians to monitor psychiatric and medical outcomes as well as treatment adherence in patients with bipolar disorder. Current depressive symptoms can be assessed with tools like the 9-item Patient Health Questionnaire or Beck Depression Inventory. Lifetime presence or absence of manic or hypomanic symptoms can be assessed using the Mood Disorder Questionnaire (MDQ). These measures can be completed quickly by patients prior to appointments. Sensitivity of such ratings, particularly the MDQ, can be increased by having a significant other also rate the patient. Clinicians should also screen mood disorder patients for psychiatric comorbidities that are common in this population such as anxiety and substance use disorders. While patients with bipolar disorder may commonly be nonadherent with prescribed medication regimens, strategies that can help include having frank discussions with the patient, selecting medication collaboratively, adding psychotherapy with a psychoeducation element, monitoring appointment-keeping, using patient self-reports of medication-taking, enlisting the aid of significant others, and measuring plasma drug levels. Medical monitoring is needed to assess the safety and tolerability of psychotropic medications. All of the approved medications for bipolar disorder have at least 1 boxed warning for serious side effects, but are also associated with other common management-limiting side effects such as sedation, tremor, unsteadiness, restlessness, nausea, vomiting, diarrhea, constipation, weight gain, and metabolic problems. Routine monitoring is particularly needed for obesity, metabolic syndrome, and cardiovascular disorders, which lead to high rates of medical morbidity and mortality in patients with bipolar disorder. Monitoring protocols such as the one recommended by the American Diabetes Association for patients taking second-generation antipsychotics can be used for regular assessment.
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PMID:Strategies for monitoring outcomes in patients with bipolar disorder. 2062 1

Multisystem atrophy is a neurologic condition defined as an adult-onset, progressive, neurodegenerative disease of unknown etiology. It carries a multisystem clinical course, including autonomic, urogenital, cerebellar, and parkinsonian features. Lithium toxicity, classically manifesting as increased thirst, polyuria, gastric distress, weight gain, tremor, fatigue, and mild cognitive impairment, can present in a similar manner.(1) We would like to present a patient diagnosed with progressive neurologic features typical of multisystem atrophy that also had bipolar disorder and had been taking lithium for many years. Despite normal lithium levels, it appeared as though a subclinical lithium toxicity was manifesting in the patient, and once lithium was discontinued, the patient was discharged from hospice with significant improvement in his presenting symptoms.
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PMID:Multisystem atrophy made worse by lithium treatment in a hospice patient: a case report. 2236 34

A previously healthy 15-year-old boy presented with a 2-week history of acute tremor in his hands, fasciculation of his tongue and a sensation that his mind was going blank. Physical examination and investigations confirmed a diagnosis of Wilson's disease and chelating treatment was started. As his neurological symptoms and liver function started to improve he developed tearfulness symptoms of depression and intense doubt about everything he thought and said. He was diagnosed with a moderate depressive episode and obsessive compulsive disorder as a result of Wilson's disease and started on citalopram. After an initial period of improvement with citalopram, his symptoms changed and he appeared irritable, restless, impulsive, disinhibited and was unable to sleep. Bipolar affective disorder was diagnosed and treatment changed to lithium carbonate and olanzepine, which led to a gradual mood stabilisation and successful recovery.
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PMID:Complex psychiatric presentation in adolescent onset Wilson's disease. 2271 18

A 42-year-old woman, with a 12-year history of bipolar disorder was referred to our department due to tremor, sedation, dysarthria, polyuria and polydipsia. She had been on lithium monotherapy during the last 3 years. On admission, her cognitive status was intact, and neither depression nor euphoria was reported. Lithium plasma levels were 1.6 mEq/L, whereas creatinine and urea levels were 2.8 IU/L and 110 IU/L, respectively. The patient did not take other medications or misused lithium. Lithium was immediately discontinued. Ultrasound scans of the urinary tract were suggestive of bilateral hydronephrosis secondary to bladder contraction and cystoscopy-guided bladder biopsy revealed glandular cystitis a benign tumour into the bladder's wall, which impeded the bladder's contraction leading to hydronephrosis and subsequent toxic lithium plasma levels. The patient was switched to valproate and was referred for surgical excision of the lesion. One year later, she was in good physical and mental health under treatment with valproate (1000 mg/day). This is the first case report of glandular cystitis leading to lithium intoxication by impairing renal function. Acute renal failure leading to lithium intoxication would be possible. However, a thorough imaging, endoscopical and histological study revealed glandular cystitis as the cause of renal impairment. Although physicians are alert about lithium's toxicity and a monitoring of renal function is routinely prescribed, little focus has been made on the integrity of the urinary tract. We suggest that urinary tract imaging should be part of the routine work-up in patients presenting with symptoms and signs of lithium intoxication, since concomitant urinary tract lesions might occasionally be the cause of renal impairment leading to reduced lithium excretion.
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PMID:Glandular cystitis and lithium intoxication in a patient with bipolar disorder. 2279 15

Lithium salts have been used in treatment of depression and bipolar disorder for more than 50 years. Neurotoxic side-effects such as nystagmus, ataxia, tremor, fasciculation, clonus, seizure and even coma have been well described in the literature. We present a case of generalised peripheral neuropathy following lithium intoxication. It is a rare presentation with delayed onset and characterised by a rapid downhill course. Diagnosis was confirmed by nerve conduction tests, which showed axonal neuropathy. Despite the profound neurological effects of this toxicity, it is readily reversible with supportive care and the prognosis is good.
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PMID:A rare neurological complication due to lithium poisoning. 2286 82


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