- Email: [email protected]
Gabapentin-induced mood changes with hypomanic features in adults
Seizure 2000; 9: 505–508
doi: 10.1053/seiz.2000.0445, available online at http://www.idealibrary.com on
CASE REPORT
Gabapentin-induced mood changes with hypomanic features in adults †
†
†
‡
¨ EUGEN TRINKA , ULRIKE NIEDERMULLER , CLAUDIA THALER , STEPHAN DOERING , TITUS § § † MORODER , GUNTHER LADURNER & GERHARD BAUER †
¨ ¨ Universitatsklinik fur fur ¨ Neurologie Innsbruck, Austria; ‡ Universitatsklinik ¨ Medizinische Psychologie und Psychotherapie Innsbruck, Austria; § Neurologische Abteilung Christian Doppler Klinik Salzburg, Austria ¨ Correspondence to: Eugen Trinka, MD, Universitatsklinik fur ¨ Neurologie, Innsbruck, Anichstrasse 35, A-6020 Innsbruck, Austria. E-mail: [email protected]
We report two adults who received gabapentin (GBP) and subsequently developed behavioural side effects. Indications for GBP treatment were newly diagnosed epilepsy in one and painful paraesthesiae in the other. Both had no past history of psychiatric or behavioural disorder. Abnormal behaviour consisted of elevated mood, euphoria, and increased energy in both patients, and pressure of speech and decreased need for sleep in one of them. These symptoms were transient and fully reversible. One patient had to discontinue GBP. Behavioural changes were not related to seizure activity. They should be recognized as a possible side effect of GBP treatment in adults. c 2000 BEA Trading Ltd
Key words: gabapentin; adverse effects; mood; hypomania; behaviour.
INTRODUCTION
Case 1
Gabapentin (GBP) is a new antiepileptic drug (AED) structurally related to γ -aminobutyric acid (GABA). GBP crosses the blood–brain barrier but is neither metabolized nor bound to plasma protein and does not affect serum concentrations of other antiepileptic drugs1 . It has been marketed as an anticonvulsant with ‘ideal’ pharmacokinetic properties, effective in adults as add-on therapy and monotherapy for epilepsies with partial seizures2–7 . GBP is also effective as add-on therapy for children aged >3 years8 . Furthermore, GBP is used in the treatment of neuropathic pain9–11 , migraine12 , erythromelalgia13, 14 and painful dysaesthesias in multiple sclerosis15 . In general, GBP is associated with very low toxicity and a favourable safety profile16 . We report two patients who exhibited behavioural problems after moderate doses of GBP.
A woman experienced her first generalized tonic– clonic seizure at the age of 37, although, since the age of 3 years, she had had attacks with a vague epigastric sensation followed by dizziness. These attacks occurred at least once or twice a month. Neurological examination, birth history, and past medical history, routine laboratory tests, cerebral computed tomography (CCT) scan, and electroencephalogram (EEG) were normal. She is of normal intelligence and does not have a past psychiatric history. She is married and works as a secretary in an office. A diagnosis of epilepsy with partial seizures with secondary generalized tonic–clonic seizures was made. We started GBP monotherapy increasing by 300 mg daily to a maintenance dose of 600 mg three times daily. After 5 days of treatment she felt unusually well and euphoric. Her husband and her colleagues at work
1059–1311/00/070505 + 04
$35.00/0
c 2000 BEA Trading Ltd
506
recognized the mood change. She was compelled to laugh in inappropriate situations and felt full of energy. She had no flight of ideas, her speech was not pressured and reportedly sleep was normal and not disrupted. The patient herself did not feel unwell, but she recognized that her inappropriate laughter and giggling impaired her functioning at work. We stopped GBP after 16 days of treatment, during which time the patient was seizure free and started with carbamazepine (CBZ). Three days later her symptoms resolved completely and her seizures have remained controlled for 2 years with CBZ. No further episodes of inappropriate behaviour have been reported.
Case 2
A 38-year-old previously healthy female was admitted to hospital because of severe thoracic pain and fatigue, which developed 2 weeks after laryngitis. A myocarditis of unknown aetiology was diagnosed. She was treated with antipyretics and bed rest. Two weeks later she experienced severe pain in her left arm, shoulder and left hemibody, accompanied by unpleasant paraesthesiae and dizziness. On neurological examination she had hemi-hypaesthesia on her left side accompanied with brisk deep tendon reflexes and a positive Babinski’s sign. There was no past psychiatric history. Past medical and family history was normal. Lumbar puncture with CSF analysis revealed intrathecal immunoglobulin M synthesis and positive antibody titres against chlamydia. A diagnosis of parainfectious encephalomyelitis was made and a 5-day treatment course with corticosteroids was initiated. The unpleasant and painful paraesthesiae were treated with GBP. We increased the dosage gradually by 300 mg a day to a maintenance dose of 300 mg t.i.d. The painful paraesthesiae resolved gradually, but a week later she experienced mood changes with euphoria, inappropriate laughter and giggling. Her husband recognized this mood change. She did not feel uncomfortable, displayed increased energy and a decreased need for sleep. Speech was not typically pressured but fast and difficult to interrupt. She had no flight of ideas and did not show increased goal-directed activity or grandiosity. The mood changes were not severe enough to cause marked impairment in functioning. Her painful paraesthesiae improved so she decided to stay on GBP. The euphoria resolved and her behaviour returned to baseline within the next 2 weeks without any change in medication.
E. Trinka et al.
DISCUSSION GBP is a new AED which is used worldwide for the treatment of epilepsies with partial seizures in adults and children >3 years, and neuropathic pain. It is known as a safe drug with desirable pharmacokinetic properties. The most common side effects in adults were somnolence, dizziness, fatigue, nausea, ataxia, and headache5, 6, 16 . Several reports of behavioural side effects of GBP in children have been published17–21 . Wolf and co-workers17 described three children with learning disabilities and intractable partial seizures who became hyperactive and had explosive outbursts consisting of aggressive and oppositional behaviour on GBP. The behavioural problems were sufficiently severe to require discontinuation of GBP despite moderately improved seizure control. Tallian et al.20 reported two children who received GBP for intractable seizures and who developed intolerable aggressive behaviour requiring dose reduction or drug discontinuation. Lee et al.18 reported seven children who received gabapentin (GBP) as adjunctive medication and subsequently developed behavioural changes consisting of intensification of baseline behavioural abnormalities as well as new behavioural problems. Behaviour which parents considered most troublesome was, tantrums, aggression directed toward others, hyperactivity, and defiance. All behavioural changes were reversible and were managed by dose reduction or discontinuation of GBP. All children had baseline attention deficit hyperactivity disorder (ADHD) or developmental delay. In adults there is only one case report of gabapentininduced behavioural change22 . This patient was mentally retarded and had refractory epilepsy. He received GBP in moderate doses and became markedly disinhibited and over familiar towards female staff on the ward, making inappropriate sexual remarks and becoming physically demonstrative. His sleep pattern was markedly disrupted. His behaviour was diagnosed as hypomania. It has been speculated23 that the episode was related to forced normalization, initially described by Landolt24 . However, a detailed description of seizure control and EEG findings were not reported. In the present series, patient no. 1 had newly diagnosed epilepsy and not chronic epilepsy. She entered seizure remission at the start of treatment with GBP and had no seizure activity after introduction of CBZ monotherapy. Patient no. 2 did not have epilepsy at all. Therefore we cannot attribute the mood changes to forced normalization in our patients. The episode of elevated mood was clearly different from the habitual mood in both patients and was recognized as abnormal by their husbands. Severity of symptoms
Gabapentin-induced mood changes in adults
did not prompt hospitalization. In patient no. 1, interference with functioning at work as a secretary was severe enough to lead to drug withdrawal. The onset of episodes was related to the start of GBP treatment and resolved gradually despite continued GBP medication in patient no. 2. We classified these episodes according to DSM-IV (292.84)25 as gabapentin-induced mood disorder with mild manic features and onset during medication. The gabapentin-induced behavioural changes in children and the mood changes with hypomanic features in adults are both characterized by excessive activity and impulsive behaviour. The behavioural changes in children are distinguished by the absence of elevated or euphoric mood. Characteristically, children with chronic epilepsy and static encephalopathy with behavioural problems (e.g. ADHD) are at risk of developing intensification of baseline behaviour or de novo behavioural problems. These side effects in children are not unique to GBP and have been reported with valproate, carbamazepine, clonazepam and phenobarbital26–29 . To date, all previously reported patients with GBPinduced behavioural changes had difficult to treat epilepsy. From these observations it is not clear whether the behavioural disturbances can be attributed to; (i) forced normalization, (ii) a direct pharmacological effect, (iii) the seizures themselves, as for example in peri-ictal psychosis30 , or (iv) intensification of baseline behavioural disorder. To our knowledge this is the first report of GBP-induced mood changes in a patient with newly diagnosed epilepsy and a patient with painful paraesthesiae. The behavioural side effects in these two patients cannot be explained by the phenomenon of forced normalization or peri-ictal psychosis nor by intensification of an underlying chronic behavioural or psychiatric disorder. Therefore we conclude that the most likely mechanism is a direct pharmacological effect of GBP. Although the severity of mood changes in our adult patients has been mild and self-limiting or reversible, clinicians should recognize the possibility of adverse behavioural changes, especially hypomania-like episodes not only in mentally handicapped children but also in adults during GBP therapy.
507
5.
6.
7.
8.
9. 10. 11.
12.
13. 14.
15.
16.
17.
18.
19.
20.
21.
REFERENCES 1. Mc Lean, M. J. Gabapentin. Epilepsia 1995; 36 (Suppl. 2): S73–S86. 2. UK Gabapentin Study Group. Gabapentin in partial epilepsy. Lancet 1990; 335: 114–117. 3. US Gabapentin Study Group No. 5. Gabapentin as add-on therapy in refractory partial epilepsy: a double-blind, placebocontrolled, parallel-group study. Neurology 1993; 43: 2292– 2298. 4. Anhut, H., Ashman, P., Feuerstein, T. J. et al. Gabapentin
22. 23.
24.
(Neurontin) as add-on therapy in patients with partial seizures: a double-blind, placebo-controlled study. Epilepsia 1994; 35: 795–801. Bergey, G. K., Morris, H. H., Rosenfeld, W. et al. Gabapentin monotherapy: I. An 8-day double blind, dose-controlled, multicenter study in hospitalized patients with refractory complex partial or secondarily generalized seizures. Neurology 1997; 49: 739–745. Beydoun, A., Fisher, J., Labar, D. R. et al. Gabapentin monotherapy: II. A 26-week, double blind, dose-controlled, multicenter study of conversion from polytherapy in outpatients with refractory complex partial seizures or secondarily generalized seizures. Neurology 1997; 49: 746–752. Chadwick, D. W., Anhut, H., Greiner, M. J. et al. A doubleblind trial of gabapentin monotherapy for newly diagnosed partial seizures. Neurology 1998; 51: 1282–1288. Appleton, R., Fichtner, K., LaMoreaux, L. et al. Gabapentin as add-on therapy in children with refractory partial seizures: a 12-week, multicentre, double-blind, placebo-controlled study. Epilepsia 1999; 40: 1147–1154. Sist, T., Filadora, V., Miner, M. et al. Gabapentin for idiopathic trigeminal neuralgia. Neurology 1998; 50: Abstract P06.012. Waldman, S. D. Tutorial 28: Evaluation and treatment of trigeminal neuralgia. Pain Digest 1997; 7: 21–24. Valzania, F., Strafella, A. P., Nasetti, S. A., Tropenai, A. and Tassinari, C. A. Gabapentin in idiopathic trigeminal neuralgia. Neurology 1998; 50: Abstract P06.012. Nicoldi, M. and Sicuteri, F. A NMDA modulator Gabapentin clearly facilitates resolution of chronic migraine. Pharmacological Research 1997; 35 (Suppl.): 64. Mc Graw, T. and Kosek, P. Erythromelalgia pain managed with gabapentin. Anesthesiology 1997; 86: 988–990. Wakim, M. E., Zelzer, L., Roberts, R. L. et al. Management of erythromelalgia with epidural bupivacain, and fentanyl and oral gabapentin. Journal of Investigative Medicine 1997; 45:138a[Abstract]. Samkoff, L. M., Daras, M., Tuchman, A. et al. Amelioration of refractory dysesthetic limb pain in multiple sclerosis by gabapentin. Neurology 1997; 49: 304–305. Anhut, H., Ashmann, P. J., Feuerstein, J. et al. Long-term safety and efficacy of Gabapentin as add-on therapy in patients with refractory partial seizures. Journal of Epilepsy 1995; 8: 44–50. Wolf, S. M., Shinnar, S., Kang, H., Gil, K. B. and Mosh´e, S. L. Gabapentin toxicity in children manifesting as behavioral changes. Epilepsia 1995; 36: 1203–1205. Lee, D. O., Steingard, R. J., Cesena, M., Helmers, S. L., Riviello, J. J. and Mikati, M. A. Behavioral side effects of gabapentin in children. Epilepsia 1996; 37: 87–90. Khurana, D. S., Riviello, J., Helmers, S., Holmes, G., Anderson, J. and Mikati, M. A. Efficacy of gabapentin therapy in children with refractory partial seizures. Journal of Pediatrics 1996; 128: 829–833. Tallian, K. B., Nahata, M. C., Lo, W. and Tsao, C. Y. Gabapentin associated with aggressive behavior in pediatric patients with seizures. Epilepsia 1996; 37: 501–502. Mikati, M. A., Choueri, R., Khurana, D. S., Riviello, J., Helmers, S. and Holmes, G. Gabapentin in the treatment of refractory partial epilepsy in children with intellectual disability. Journal of Intellectual Disability Research 1998; 42 (Suppl.): 57–62. Short, C. and Cooke, L. Hypomania induced by gabapentin. British Journal of Psychiatry 1995; 166: 679–680. Hauck, A. and Bhaumik, S. Hypomania induced by Gabapentin. (Comment). British Journal of Psychiatry 1995; 167: 549. ¨ Landolt, H. Uber Verstimmungen, D¨ammerzust¨ande und schizophrene Zustandsbilder bei Epilepsie. Ergebnisse klinischer und elektroencephalographischer Untersuchungen. Schweizer Archiv fur Neurologie und Psychiatrie 1955; 76:
508 313–321. 25. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4th Edition. Washington, American Psychiatric Association, 1994. 26. Rivinius, T. M. Psychiatric effects of the anticonvulsant regimens. Journal of Clinical Psychopharmacology 1982; 2: 165– 192. 27. Wolf, S. M. and Forsythe, A. Behavior disturbance, phenobarbital and febrile seizures. Pediatrics 1978; 61: 728–731.
E. Trinka et al. 28. Committee on Drugs. Behavioral and cognitive side effects of anticonvulsant therapy. Pediatrics 1985; 76: 644–677. 29. Silverstein, F. S., Parrish, M. A. and Johnston, M. V. Adverse behavioral reactions in children treated with carbamazepine (Tegretol). Journal of Pediatrics 1982; 101: 785–787. 30. Wolf, P. Psychosen bei Epilepsie. Ihre Bedingungen und Wechselbeziehungen zu Anf¨allen, Thesis, Freie Universit¨at Berlin, 1976.
doi: 10.1053/seiz.2000.0445, available online at http://www.idealibrary.com on
CASE REPORT
Gabapentin-induced mood changes with hypomanic features in adults †
†
†
‡
¨ EUGEN TRINKA , ULRIKE NIEDERMULLER , CLAUDIA THALER , STEPHAN DOERING , TITUS § § † MORODER , GUNTHER LADURNER & GERHARD BAUER †
¨ ¨ Universitatsklinik fur fur ¨ Neurologie Innsbruck, Austria; ‡ Universitatsklinik ¨ Medizinische Psychologie und Psychotherapie Innsbruck, Austria; § Neurologische Abteilung Christian Doppler Klinik Salzburg, Austria ¨ Correspondence to: Eugen Trinka, MD, Universitatsklinik fur ¨ Neurologie, Innsbruck, Anichstrasse 35, A-6020 Innsbruck, Austria. E-mail: [email protected]
We report two adults who received gabapentin (GBP) and subsequently developed behavioural side effects. Indications for GBP treatment were newly diagnosed epilepsy in one and painful paraesthesiae in the other. Both had no past history of psychiatric or behavioural disorder. Abnormal behaviour consisted of elevated mood, euphoria, and increased energy in both patients, and pressure of speech and decreased need for sleep in one of them. These symptoms were transient and fully reversible. One patient had to discontinue GBP. Behavioural changes were not related to seizure activity. They should be recognized as a possible side effect of GBP treatment in adults. c 2000 BEA Trading Ltd
Key words: gabapentin; adverse effects; mood; hypomania; behaviour.
INTRODUCTION
Case 1
Gabapentin (GBP) is a new antiepileptic drug (AED) structurally related to γ -aminobutyric acid (GABA). GBP crosses the blood–brain barrier but is neither metabolized nor bound to plasma protein and does not affect serum concentrations of other antiepileptic drugs1 . It has been marketed as an anticonvulsant with ‘ideal’ pharmacokinetic properties, effective in adults as add-on therapy and monotherapy for epilepsies with partial seizures2–7 . GBP is also effective as add-on therapy for children aged >3 years8 . Furthermore, GBP is used in the treatment of neuropathic pain9–11 , migraine12 , erythromelalgia13, 14 and painful dysaesthesias in multiple sclerosis15 . In general, GBP is associated with very low toxicity and a favourable safety profile16 . We report two patients who exhibited behavioural problems after moderate doses of GBP.
A woman experienced her first generalized tonic– clonic seizure at the age of 37, although, since the age of 3 years, she had had attacks with a vague epigastric sensation followed by dizziness. These attacks occurred at least once or twice a month. Neurological examination, birth history, and past medical history, routine laboratory tests, cerebral computed tomography (CCT) scan, and electroencephalogram (EEG) were normal. She is of normal intelligence and does not have a past psychiatric history. She is married and works as a secretary in an office. A diagnosis of epilepsy with partial seizures with secondary generalized tonic–clonic seizures was made. We started GBP monotherapy increasing by 300 mg daily to a maintenance dose of 600 mg three times daily. After 5 days of treatment she felt unusually well and euphoric. Her husband and her colleagues at work
1059–1311/00/070505 + 04
$35.00/0
c 2000 BEA Trading Ltd
506
recognized the mood change. She was compelled to laugh in inappropriate situations and felt full of energy. She had no flight of ideas, her speech was not pressured and reportedly sleep was normal and not disrupted. The patient herself did not feel unwell, but she recognized that her inappropriate laughter and giggling impaired her functioning at work. We stopped GBP after 16 days of treatment, during which time the patient was seizure free and started with carbamazepine (CBZ). Three days later her symptoms resolved completely and her seizures have remained controlled for 2 years with CBZ. No further episodes of inappropriate behaviour have been reported.
Case 2
A 38-year-old previously healthy female was admitted to hospital because of severe thoracic pain and fatigue, which developed 2 weeks after laryngitis. A myocarditis of unknown aetiology was diagnosed. She was treated with antipyretics and bed rest. Two weeks later she experienced severe pain in her left arm, shoulder and left hemibody, accompanied by unpleasant paraesthesiae and dizziness. On neurological examination she had hemi-hypaesthesia on her left side accompanied with brisk deep tendon reflexes and a positive Babinski’s sign. There was no past psychiatric history. Past medical and family history was normal. Lumbar puncture with CSF analysis revealed intrathecal immunoglobulin M synthesis and positive antibody titres against chlamydia. A diagnosis of parainfectious encephalomyelitis was made and a 5-day treatment course with corticosteroids was initiated. The unpleasant and painful paraesthesiae were treated with GBP. We increased the dosage gradually by 300 mg a day to a maintenance dose of 300 mg t.i.d. The painful paraesthesiae resolved gradually, but a week later she experienced mood changes with euphoria, inappropriate laughter and giggling. Her husband recognized this mood change. She did not feel uncomfortable, displayed increased energy and a decreased need for sleep. Speech was not typically pressured but fast and difficult to interrupt. She had no flight of ideas and did not show increased goal-directed activity or grandiosity. The mood changes were not severe enough to cause marked impairment in functioning. Her painful paraesthesiae improved so she decided to stay on GBP. The euphoria resolved and her behaviour returned to baseline within the next 2 weeks without any change in medication.
E. Trinka et al.
DISCUSSION GBP is a new AED which is used worldwide for the treatment of epilepsies with partial seizures in adults and children >3 years, and neuropathic pain. It is known as a safe drug with desirable pharmacokinetic properties. The most common side effects in adults were somnolence, dizziness, fatigue, nausea, ataxia, and headache5, 6, 16 . Several reports of behavioural side effects of GBP in children have been published17–21 . Wolf and co-workers17 described three children with learning disabilities and intractable partial seizures who became hyperactive and had explosive outbursts consisting of aggressive and oppositional behaviour on GBP. The behavioural problems were sufficiently severe to require discontinuation of GBP despite moderately improved seizure control. Tallian et al.20 reported two children who received GBP for intractable seizures and who developed intolerable aggressive behaviour requiring dose reduction or drug discontinuation. Lee et al.18 reported seven children who received gabapentin (GBP) as adjunctive medication and subsequently developed behavioural changes consisting of intensification of baseline behavioural abnormalities as well as new behavioural problems. Behaviour which parents considered most troublesome was, tantrums, aggression directed toward others, hyperactivity, and defiance. All behavioural changes were reversible and were managed by dose reduction or discontinuation of GBP. All children had baseline attention deficit hyperactivity disorder (ADHD) or developmental delay. In adults there is only one case report of gabapentininduced behavioural change22 . This patient was mentally retarded and had refractory epilepsy. He received GBP in moderate doses and became markedly disinhibited and over familiar towards female staff on the ward, making inappropriate sexual remarks and becoming physically demonstrative. His sleep pattern was markedly disrupted. His behaviour was diagnosed as hypomania. It has been speculated23 that the episode was related to forced normalization, initially described by Landolt24 . However, a detailed description of seizure control and EEG findings were not reported. In the present series, patient no. 1 had newly diagnosed epilepsy and not chronic epilepsy. She entered seizure remission at the start of treatment with GBP and had no seizure activity after introduction of CBZ monotherapy. Patient no. 2 did not have epilepsy at all. Therefore we cannot attribute the mood changes to forced normalization in our patients. The episode of elevated mood was clearly different from the habitual mood in both patients and was recognized as abnormal by their husbands. Severity of symptoms
Gabapentin-induced mood changes in adults
did not prompt hospitalization. In patient no. 1, interference with functioning at work as a secretary was severe enough to lead to drug withdrawal. The onset of episodes was related to the start of GBP treatment and resolved gradually despite continued GBP medication in patient no. 2. We classified these episodes according to DSM-IV (292.84)25 as gabapentin-induced mood disorder with mild manic features and onset during medication. The gabapentin-induced behavioural changes in children and the mood changes with hypomanic features in adults are both characterized by excessive activity and impulsive behaviour. The behavioural changes in children are distinguished by the absence of elevated or euphoric mood. Characteristically, children with chronic epilepsy and static encephalopathy with behavioural problems (e.g. ADHD) are at risk of developing intensification of baseline behaviour or de novo behavioural problems. These side effects in children are not unique to GBP and have been reported with valproate, carbamazepine, clonazepam and phenobarbital26–29 . To date, all previously reported patients with GBPinduced behavioural changes had difficult to treat epilepsy. From these observations it is not clear whether the behavioural disturbances can be attributed to; (i) forced normalization, (ii) a direct pharmacological effect, (iii) the seizures themselves, as for example in peri-ictal psychosis30 , or (iv) intensification of baseline behavioural disorder. To our knowledge this is the first report of GBP-induced mood changes in a patient with newly diagnosed epilepsy and a patient with painful paraesthesiae. The behavioural side effects in these two patients cannot be explained by the phenomenon of forced normalization or peri-ictal psychosis nor by intensification of an underlying chronic behavioural or psychiatric disorder. Therefore we conclude that the most likely mechanism is a direct pharmacological effect of GBP. Although the severity of mood changes in our adult patients has been mild and self-limiting or reversible, clinicians should recognize the possibility of adverse behavioural changes, especially hypomania-like episodes not only in mentally handicapped children but also in adults during GBP therapy.
507
5.
6.
7.
8.
9. 10. 11.
12.
13. 14.
15.
16.
17.
18.
19.
20.
21.
REFERENCES 1. Mc Lean, M. J. Gabapentin. Epilepsia 1995; 36 (Suppl. 2): S73–S86. 2. UK Gabapentin Study Group. Gabapentin in partial epilepsy. Lancet 1990; 335: 114–117. 3. US Gabapentin Study Group No. 5. Gabapentin as add-on therapy in refractory partial epilepsy: a double-blind, placebocontrolled, parallel-group study. Neurology 1993; 43: 2292– 2298. 4. Anhut, H., Ashman, P., Feuerstein, T. J. et al. Gabapentin
22. 23.
24.
(Neurontin) as add-on therapy in patients with partial seizures: a double-blind, placebo-controlled study. Epilepsia 1994; 35: 795–801. Bergey, G. K., Morris, H. H., Rosenfeld, W. et al. Gabapentin monotherapy: I. An 8-day double blind, dose-controlled, multicenter study in hospitalized patients with refractory complex partial or secondarily generalized seizures. Neurology 1997; 49: 739–745. Beydoun, A., Fisher, J., Labar, D. R. et al. Gabapentin monotherapy: II. A 26-week, double blind, dose-controlled, multicenter study of conversion from polytherapy in outpatients with refractory complex partial seizures or secondarily generalized seizures. Neurology 1997; 49: 746–752. Chadwick, D. W., Anhut, H., Greiner, M. J. et al. A doubleblind trial of gabapentin monotherapy for newly diagnosed partial seizures. Neurology 1998; 51: 1282–1288. Appleton, R., Fichtner, K., LaMoreaux, L. et al. Gabapentin as add-on therapy in children with refractory partial seizures: a 12-week, multicentre, double-blind, placebo-controlled study. Epilepsia 1999; 40: 1147–1154. Sist, T., Filadora, V., Miner, M. et al. Gabapentin for idiopathic trigeminal neuralgia. Neurology 1998; 50: Abstract P06.012. Waldman, S. D. Tutorial 28: Evaluation and treatment of trigeminal neuralgia. Pain Digest 1997; 7: 21–24. Valzania, F., Strafella, A. P., Nasetti, S. A., Tropenai, A. and Tassinari, C. A. Gabapentin in idiopathic trigeminal neuralgia. Neurology 1998; 50: Abstract P06.012. Nicoldi, M. and Sicuteri, F. A NMDA modulator Gabapentin clearly facilitates resolution of chronic migraine. Pharmacological Research 1997; 35 (Suppl.): 64. Mc Graw, T. and Kosek, P. Erythromelalgia pain managed with gabapentin. Anesthesiology 1997; 86: 988–990. Wakim, M. E., Zelzer, L., Roberts, R. L. et al. Management of erythromelalgia with epidural bupivacain, and fentanyl and oral gabapentin. Journal of Investigative Medicine 1997; 45:138a[Abstract]. Samkoff, L. M., Daras, M., Tuchman, A. et al. Amelioration of refractory dysesthetic limb pain in multiple sclerosis by gabapentin. Neurology 1997; 49: 304–305. Anhut, H., Ashmann, P. J., Feuerstein, J. et al. Long-term safety and efficacy of Gabapentin as add-on therapy in patients with refractory partial seizures. Journal of Epilepsy 1995; 8: 44–50. Wolf, S. M., Shinnar, S., Kang, H., Gil, K. B. and Mosh´e, S. L. Gabapentin toxicity in children manifesting as behavioral changes. Epilepsia 1995; 36: 1203–1205. Lee, D. O., Steingard, R. J., Cesena, M., Helmers, S. L., Riviello, J. J. and Mikati, M. A. Behavioral side effects of gabapentin in children. Epilepsia 1996; 37: 87–90. Khurana, D. S., Riviello, J., Helmers, S., Holmes, G., Anderson, J. and Mikati, M. A. Efficacy of gabapentin therapy in children with refractory partial seizures. Journal of Pediatrics 1996; 128: 829–833. Tallian, K. B., Nahata, M. C., Lo, W. and Tsao, C. Y. Gabapentin associated with aggressive behavior in pediatric patients with seizures. Epilepsia 1996; 37: 501–502. Mikati, M. A., Choueri, R., Khurana, D. S., Riviello, J., Helmers, S. and Holmes, G. Gabapentin in the treatment of refractory partial epilepsy in children with intellectual disability. Journal of Intellectual Disability Research 1998; 42 (Suppl.): 57–62. Short, C. and Cooke, L. Hypomania induced by gabapentin. British Journal of Psychiatry 1995; 166: 679–680. Hauck, A. and Bhaumik, S. Hypomania induced by Gabapentin. (Comment). British Journal of Psychiatry 1995; 167: 549. ¨ Landolt, H. Uber Verstimmungen, D¨ammerzust¨ande und schizophrene Zustandsbilder bei Epilepsie. Ergebnisse klinischer und elektroencephalographischer Untersuchungen. Schweizer Archiv fur Neurologie und Psychiatrie 1955; 76:
508 313–321. 25. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4th Edition. Washington, American Psychiatric Association, 1994. 26. Rivinius, T. M. Psychiatric effects of the anticonvulsant regimens. Journal of Clinical Psychopharmacology 1982; 2: 165– 192. 27. Wolf, S. M. and Forsythe, A. Behavior disturbance, phenobarbital and febrile seizures. Pediatrics 1978; 61: 728–731.
E. Trinka et al. 28. Committee on Drugs. Behavioral and cognitive side effects of anticonvulsant therapy. Pediatrics 1985; 76: 644–677. 29. Silverstein, F. S., Parrish, M. A. and Johnston, M. V. Adverse behavioral reactions in children treated with carbamazepine (Tegretol). Journal of Pediatrics 1982; 101: 785–787. 30. Wolf, P. Psychosen bei Epilepsie. Ihre Bedingungen und Wechselbeziehungen zu Anf¨allen, Thesis, Freie Universit¨at Berlin, 1976.