AboutIvan Goldberg, M.D. Expertise I am a psychiatrist/psychopharmacologist with many years of expereince in treating individuals with depressions, manic-depression (Bipolar Disorder), other mood disorders,. I am especially interested in the psychopharmacologic treatment of individuals with so called "treatment-resistant" syndromes.
Experience I have been on the staff of the National Institute of Mental Health, Columbia's College of Physicians and Surgeons, and the Columbia-Presbyterian Medical Center. I am currently in full-time private practice in New York City.
A.B. Johns Hopkins University M.D. N.Y.U. College of Medicine
I am the creator of Depression Central:http://www.psycom.net/depression.central.html
Question Hello- I am taking 150mg lamotrigine/generic lamictal for bipolarII. I understand the medication binds with the eye-can this case permanent vision changes that would not go away after medication is dicontinued? I cannot seem to find any literature addressing this concern. Also, I have read and heard Lamotrigine can cause a loss of some nutrients such as potassium, but I cannot afford the name brand supplement my doctor wanted to prescribe. Is there an alternative to make up for the losses Lamotrigine causes?
Answer I have not run into any visual problems in patients I have treated with Lamictal. A search of PubMed using the search term "Lamictal and Vision" turned up the following:
1: Epilepsy Res. 2008 Feb;78(2-3):140-6. Epub 2007 Dec 21.Related Articles, Links
Relative influences of adjunctive topiramate and adjunctive lamotrigine on scanning and the effective field of view.
Profile Associates, Chapel Hill, NC, United States. profiler@intrex.net
A subsample of 67 adult patients with partial seizures participating in a randomized, double-blind study comparing the cognitive effects of adjunctive lamotrigine (LTG) and adjunctive topiramate (TPM) was administered Performance On-Line (POL) in addition to a battery of neuropsychological tests at baseline, week 8 and week 16 of treatment. The POL is a self-administered computer task that measures scanning, divided-attention, and the effective field of view. Although the POL does not measure driving performance, POL scores are correlated with driving performance. The results show that adjunctive TPM, but not adjunctive LTG, negatively impacted cognition. Both simple target identification and divided-attention performance on POL were compromised in the TPM group but not in the LTG group. The relative POL impairment associated with chronic TPM treatment was similar to that observed with the acute effects of alcohol with a breath level of .045% or a low dose of alprazolam (0.5mg). Thus, driving-related visual and cognitive skills were compromised by adjunctive TPM treatment. Therapeutic doses of adjunctive TPM pose a potential risk of impaired scanning and divided-attention skills.
Publication Types:
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Verrotti A, Manco R, Matricardi S, Franzoni E, Chiarelli F.
Department of Pediatrics, University of Chieti, Chieti, Italy. averrott@unich.it
Antiepileptic drugs are known to result in visual disturbances. A number of antiepileptic drugs have recently been reported to result in various abnormalities of vision, particularly deficiencies in visual fields and color vision. Moreover, there has been a marked improvement in the diagnosis and understanding of the pathophysiology of visual disturbance. This review collects evidence for visual adverse effects induced by the older antiepileptic drugs (barbiturates, benzodiazepine, carbamazepine, valproic acid, ethosuximide, and phenytoin) and the newer ones (vigabatrin, topiramate, tiagabine, levetiracetam, lamotrigine, gabapentin, felbamate, and oxcarbazepine).
4: Eur J Clin Pharmacol. 2007 Apr;63(4):409-15. Epub 2007 Feb 16.Related Articles, Links
Use and safety profile of antiepileptic drugs in Italy.
Iorio ML, Moretti U, Colcera S, Magro L, Meneghelli I, Motola D, Rivolta AL, Salvo F, Velo GP.
Clinical Pharmacology Unit, Reference Centre for Education and Communication within the WHO Programme for International Drug Monitoring, University of Verona, Verona, Italy.
OBJECTIVE: To analyse and discuss the use and the safety profile of individual antiepileptic drugs (AEDs) in Italy. METHODS: The AED safety data referred to the period January 1988-June 2005 and were obtained from the database of the Italian Interregional Group of Pharmacovigilance (GIF). This database collects all spontaneous reports of suspected adverse drug reactions (ADRs) from six Italian regions which are the main contributors to the Italian spontaneous reporting system. Individual AED consumption data (defined daily dose/1,000 inhabitants per day) in the GIF area and in the whole of Italy referred to the period January 2003-June 2005 and were derived from drug sales data (Institute for Medical Statistics Health). RESULTS: Phenobarbital was the most frequently used AED in the GIF area (4.26 DDD/1,000 inhabitants per day) followed by carbamazepine (1.97), valproic acid (1.33) and gabapentin (1.10). AED consumption in the whole of Italy showed a similar pattern. Gabapentin was the most frequently used AED among newer AEDs. In the GIF database 37,906 reports (up to June 2005) were present; 666 of them (1.76%) were associated with at least one AED (Anatomical Therapeutic Chemical code N03A). The AED with the highest number of reports was carbamazepine (208 reports) followed by phenobarbital (98), gabapentin (80), phenytoin (56), valproic acid (55), lamotrigine (51), oxcarbazepine (43) and vigabatrin (35). Use and toxicity profile were evaluated only for AEDs associated with at least 30 reports. Skin reactions were the most frequently reported ADRs, followed by haematological, general condition, hepatic, neurological and gastrointestinal adverse reactions. Phenobarbital, lamotrigine, carbamazepine and phenytoin had the highest percentage of skin reactions (69, 67, 60 and 54%, respectively). Many haematological reactions were reported for each AED; the highest percentage was related to valproic acid (25%). Vigabatrin was associated with the highest percentage of reactions related to hearing, vision and other senses (97%). Phenytoin and valproic acid had the highest percentage of hepatic reactions (30 and 20%), whereas gabapentin of nervous system, psychiatric, gastrointestinal and urinary reactions (26, 21, 21 and 14%, respectively) and phenobarbital of musculoskeletal reactions (13%). CONCLUSIONS: In Italy antiepileptic drug therapy appears to be still dominated by traditional drugs. Our analysis showed a different safety profile related to each AED. Some of the drug-adverse reaction associations discussed are not included in the Italian drug leaflets or have not been reported before in the literature.
5: Prog Neuropsychopharmacol Biol Psychiatry. 2006 Mar;30(2):239-43. Epub 2005 Nov 21.Related Articles, Links
Effects of clozapine plus lamotrigine on phencyclidine-induced hyperactivity.
Williams HJ, Zamzow CR, Robertson H, Dursun SM.
Department of Pharmacology, Dalhousie University, Halifax, NS, Canada B3H 4H7.
There is growing evidence from both uncontrolled and controlled clinical studies that lamotrigine (LTG) significantly augments clozapine (CLZ) in the treatment of refractory schizophrenia (RS) [Dursun, S.M., McIntosh, D., Milliken, H., 1999. Clozapine plus lamotrigine in treatment-resistant schizophrenia. Arch. Gen. Psychiatry 56, 950; Dursun, S.M., Deakin, J.F.W., 2001. Augmenting antipsychotic treatment with lamotrigine or topiramate in patients with treatment-resistant schizophrenia: a naturalistic case-series outcome study. J. Psychopharmacol. 15, 297-301; Tiihonen, J., Hallikainen, T., Ryynanen, O.P., Repo-Tiihonen, E., Kotilinen, I., Eronen, M., Toivonen, P., Wahlbeck, K., Putkonen, A., 2003. Lamotrigine in treatment-resistant schizophrenia; a randomized placebo-controlled cross over trial. Biol. Psychiatry 54, 1241-1248; Kremer, I., Vass, A., Gorelik, I., Bar, G., Blanaru, M., Javitt, D.C., Heresco-Levy, U., 2004. Placebo-controlled trial of lamotrigine added to conventional and atypical antipsychotics in schizophrenia. Biol. Psychiatry. 56, 441-446]. However, the precise mechanism of action of this synergistic augmentation between clozapine and lamotrigine remains unclear. Therefore, the goal of this research is to explore the mechanism of action of this synergistic interaction between CLZ and LTG, utilizing a pharmacological animal model of schizophrenia by using phencyclidine (PCP). The effects of CLZ plus LTG were assessed by measuring PCP-induced hyper-locomotion and stereotyped behaviours in rats. Adult male rats (250-300 g) were pre-treated via intra-peritoneal (i.p.) injection with vehicle or drug 30 min before a PCP (5 mg/kg) or saline challenge. The behaviours were recorded and analysed for a 90-min period using the Etho Vision-computer based system. PCP produced hyper-locomotion, which was maximal at 30 min. LTG (10 mg/kg) significantly increased hyperlocomotion induced with PCP. However, a combination treatment of CLZ (5 mg/kg) plus LTG (10 mg/kg) significantly blocked the potentiation of PCP-induced hyper-locomotion observed with LTG (10 mg/kg) alone. Furthermore, the PCP-induced locomotion in the combination CLZ plus LTG-treated rats was significantly decreased when compared to vehicle. Therefore, LTG at doses that do not induce ataxia enhanced PCP-induced hyper-locomotion in rats, whereas the combination of LTG and CLZ significantly decreased PCP-induced hyper-locomotion consistent with clinical data.
Ophtalmologie Hôpital Gui de Chauliac, F-34295 Montpellier cedex 05, France. c-arndt@chu-montpellier.fr
PURPOSE: To evaluate the effects on vision in patients receiving lamotrigine (LTG) monotherapy. METHODS: Twenty-four consecutive patients taking LTG for partial seizures were referred for a routine ophthalmologic examination including visual acuity testing, tonometry, slit lamp, and fundus examination. Automated kinetic perimetry, electrooculogram (EOG), and electroretinogram were performed after informed consent was obtained. RESULTS: In 18 patients finally included, the clinical ophthalmologic examination showed no abnormality. Four patients complained of blurring; among them, one patient had a visual field constriction in both eyes, which, however, was of unclear clinical significance (poor compliance) and a reduced light/dark ratio of the electrooculogram. One other patient with blurred vision had a reduced EOG, but the visual field was normal. Two patients had a reduced EOG but no visual symptoms. Considering the whole group of patients receiving LTG therapy, the light/dark ratio of the EOG was reduced in a dose-dependent fashion (p < 0.0001). The electroretinogram was normal in all patients. CONCLUSIONS: No irreversible visual field impairment in patients treated with LTG was encountered, although a dose-dependent retinal toxicity may have been present. The exact cellular mechanism of the electrophysiologic changes in patients taking LTG remain to be explained.
Publication Types:
Comparative Study
Research Support, Non-U.S. Gov't
7: J Clin Endocrinol Metab. 2005 Aug;90(8):4936-45. Epub 2005 May 17.Related Articles, Links
CLINICAL REVIEW: Use of antiepileptic drugs in the treatment of chronic painful diabetic neuropathy.
Vinik A.
Diabetes Research Institute, 855 West Brambleton Avenue, Norfolk, Virginia 23510, USA. vinikal@evmsmail.evms.edu
CONTEXT: Up to 25% of individuals with diabetes develop painful diabetic neuropathy, suffering spontaneous pain, allodynia, hyperalgesia, and other unpleasant symptoms. Decreased physical activity, increased fatigue, and mood and sleep problems may result. EVIDENCE ACQUISITION: A MEDLINE search was conducted, limiting searching to double-blind, randomized, controlled trials (1978 to present) of antiepileptic drugs (carbamazepine, gabapentin, pregabalin, topiramate, and lamotrigine) used in the treatment of chronic neuropathic pain. EVIDENCE SYNTHESIS: The most important aspect of treatment is targeted at modification of the underlying disease. However, approaches to symptomatic pain control are essential and include multiple drug classes. Tricyclic antidepressants, including imipramine, nortriptyline, and amitriptyline, have been the mainstays of treatment, but anticholinergic effects, such as dry mouth, blurring of vision, constipation, orthostatic hypotension, and cardiac arrhythmias, as well as other adverse effects, often limit their use. Other treatments include capsaicin, clonidine, acupuncture, and electrical stimulation, suggesting that there is no single effective treatment. First-generation antiepileptic drugs have been shown to be effective in neuropathic pain. The evidence supporting the use of a new generation of antiepileptic drugs in painful diabetic neuropathy is reviewed.
Publication Types:
Research Support, Non-U.S. Gov't
Review
8: Klin Monatsbl Augenheilkd. 2004 May;221(5):395-7.Related Articles, Links
Free autologous buccal mucosal graft transplantation to treat ocular complications after toxic epidermal necrolysis: case report.
Haefliger IO, Vysniauskiene I, Pimentel AR, Soares EJ, Piffaretti JM.
Department of Eyelid and Lacrimal Surgery, University Eye Clinic, Basel, Switzerland.
BACKGROUND: Toxic epidermal necrolysis (TEN) can lead to ocular surface scarring associated with pain, dry eye symptoms, and decreased visual acuity that often are difficult to treat. HISTORY AND SIGNS: A 34-year-old woman was referred to our department two-years after TEN induced by lamotrigin (lamictal(R)). She was complaining of severe visual acuity loss, pain, and dry eye symptoms. Visual acuity was reduced to light perception in the right eye (RE) and to 0.2 in left eye (LE). Basal Schirmer test was 2 mm in RE and 3 mm in LE. With or without therapeutic contact lenses, the patient was experiencing severe discomfort requiring tear supplementation up to 50 - 80 times/day in both eyes. THERAPY AND OUTCOME: A free autologous mucosal graft (3.5 x 2.0 cm) was transplanted from the lower lip into the upper RE fornix. Six months after surgery, with therapeutic contact lenses, the need for tear supplementation was markedly reduced to 3 - 4 times/day in RE while it remained unchanged in LE. In RE, slit-lamp examination revealed decreases in the corneal stromal edema and in the diameter of neo-vessels associated with an improvement of visual acuity (counting fingers at 30 cm). Basal Schirmer test values were unchanged. It has to be mentioned that the improvement observed after surgery was markedly dependent on wearing a therapeutic contact lens. CONCLUSIONS: Free autologous buccal graft transplantation (with its presumably accessory salivary glands) in association with the use of a therapeutic contact lens can be an efficient approach to treat ocular complication following drug-induced TEN (Lyell's syndrome).
9: Clin Experiment Ophthalmol. 2003 Dec;31(6):541-3.Related Articles, Links
Visual loss in a patient with lamotrigine-induced cicatrizing conjunctivitis.
Division of Neuropharmacology, Dent Neurologic Institute, Millard Fillmore Hospital, Buffalo, NY 14209, USA.
Lamotrigine is a novel antiepileptic that, although its mechanism is not completely understood, appears to affect voltage-activated sodium channels, resulting in inhibition of the presynaptic release of the excitatory neurotransmitter glutamate. It is well absorbed after oral administration. Its route of elimination is hepatic glucuronidation, which is susceptible to both hepatic microsomal enzyme-inducing and -inhibiting agents. In clinical trials lamotrigine was effective as add-on therapy for refractory partial seizures in adults. Small trials suggest the feasibility of monotherapy, but further controlled trials are warranted to support this practice. Additional data indicate the utility of lamotrigine for generalized seizures. Reported side effects are rash, nausea, vomiting, blurred vision, diplopia, and vision abnormalities. Lamotrigine appears to be an attractive alternative to currently available antiepileptics.