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Clinical experience using gabapentin adjunctively in patients with a history of mania or hypomania
Journal of Affective Disorders 49 (1998) 229–233
Preliminary communication
Clinical experience using gabapentin adjunctively in patients with a history of mania or hypomania James Knoll, Kristine Stegman, Trisha Suppes* University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA Received 9 September 1997; accepted 2 October 1997
Abstract Background: Gabapentin is an anticonvulsant proposed to have mood-stabilizing properties. It has been effective in the add-on treatment of refractory partial seizures and secondary generalized tonic–clonic seizures. It has the advantage of a favorable side effect profile and lack of drug interactions. Methods: Twelve consecutive outpatients with persistent, treatment-resistant bipolar spectrum disorders were treated with gabapentin in combination with other medications. Patients were started at 300 mg / day, which was titrated according to clinical response. Response was assessed every 3–4 weeks with a Clinical Global Improvement Scale. Dosage and side effects were noted. The median peak dose was 2400 mg / day. Results: One patient had a marked response to gabapentin; seven, a moderate response; two, mild; and two, no response to treatment. Six patients discontinued treatment due to somatic complaints (i.e., sedation or fatigue). The most frequently reported adverse effect was sedation. Limitations: Gabapentin was added openly, and rating was nonblind in this case series. The use of concomitant medications could have increased the amount of sedation experienced with gabapentin. Conclusion: Overall, gabapentin was associated with moderate improvement of mood symptoms. Given the severity and chronicity of these patients’ illness, a moderate response must be considered a relative success. Controlled studies of gabapentin are needed to clarify its role in the treatment of bipolar disorder. 1998 Elsevier Science B.V. Keywords: Bipolar disorder; Treatment; Anticonvulsants; Mood lability; Gabapentin
1. Introduction The utility of antiepileptic drugs (AEDs) in treating bipolar disorder is an area of intensive study. Gabapentin is a newer AED effective for refractory partial seizures and secondary generalized tonic– clonic seizures. Among the advantages of this drug *Corresponding author. Tel.: 1 1 214 6484211; fax: 1 1 214 6484278.
are a favorable side effect profile and a lack of drug interactions with other AEDs (McLean, 1994; Radulovic et al., 1994). Gabapentin was synthesized to be a g-amino butyric acid (GABA) structural analog; however, no direct effects on GABA pharmacology have been shown (McLean, 1994). Its pharmacokinetics are unique in that it is rapidly absorbed, not protein bound, and is eliminated unmetabolized in the urine (McLean, 1994).
0165-0327 / 98 / $19.00 1998 Elsevier Science B.V. All rights reserved. PII S0165-0327( 98 )00027-5
230
J. Knoll et al. / Journal of Affective Disorders 49 (1998) 229 – 233
There currently are limited data on the psychiatric effects of gabapentin. One case report (Ryback and Ryback, 1995) suggests that gabapentin may be useful for the treatment of behavioral dyscontrol. Bennett et al. (1997) report antimanic efficacy in inpatients with bipolar disorder; however, Short and Cooke (1995) report hypomanic symptoms that may have been induced by gabapentin. This case series reports our clinical experience with gabapentin in 12 consecutive symptomatic patients with a history of mania or hypomania.
tioning (GAF) scale, as outlined in DSM-IV. A mild response generally indicated little or no improvement was seen, and GAF score increase of less than 10 points. A moderate response was generally associated with a 10–20 point improvement, and a marked response was greater than a 20 point improvement. The determination of treatment response was made when each patient had been stabilized at his or her maximal effective dose. Peak dose, total duration of treatment, and adverse effects were recorded.
3. Results 2. Methods Twelve outpatients with persistent, disabling symptoms of mania or hypomania and exhibiting treatment resistance to therapeutic levels of standard mood stabilizers, treatment intolerance, or both, were treated with gabapentin. The mean age of the patients was 42 years (range 30–52). Ten patients were women. All had chronic psychiatric illness, including bipolar I disorder (n 5 10), bipolar II disorder (n 5 1), and schizoaffective, bipolar type (n 5 1). Due to the treatment resistant, chronically ill nature of these patients, most were on concomitant psychotropic agents. Patients were given a starting dose of 300 mg per day and titrated according to clinical response. Individual titration schedules varied, depending upon the patient’s response and tolerance to the drug. Response to gabapentin was assessed every 3–4 weeks with a Clinical Global Improvement Scale (CGI). Each patient was assessed by the same physician at all visits. Treatment response was described as marked, moderate, mild, or no response. At the patients’ first visit, they were given an initial score according to the CGI. A score of 2–3 indicates mild illness, a score of 4–5 indicates moderate illness, and a score of 6–7 indicates marked illness. Throughout the study, patients were evaluated with CGI Improvement Scale, where a score of 1–2 indicated marked improvement, a score of 3 indicated moderate improvement, a score of 4 indicated mild improvement, and a score of 5 or greater indicated no improvement (Guy, 1976). Throughout the study, patients’ clinical progress was also evaluated using the 0–100 Global Assessment of Func-
Treatment duration ranged 3–60 weeks and peak dosages ranged 900–3300 mg / day (median dose 5 2400 mg / day). Titration schedules varied due to differences in patient tolerance. One patient had a marked response to gabapentin, during which manic symptoms and CGI were significantly improved (Table 1). Seven patients had moderate responses, two had mild responses, and two had no response to treatment. Treatment was discontinued in seven patients. Patient [ 2 developed mild alopecia and patient [ 3 dropped out due to a possible pregnancy. Seven (58%) patients reported sedation or fatigue, and five (42%) chose to discontinue treatment as a result of these adverse effects ([ 1, 7, 8, 10, 11). The following cases describe one patient with a marked response and another with a mild response: Case 1. Ms. A, a 44 year old woman ([5) with bipolar disorder I, mixed episode, previously failed a trial of combined valproate and lithium therapy. When gabapentin was initiated, the patient was on a regimen of clozapine 325 mg, valproate 1000 mg, and clonazepam 2 mg daily. Gabapentin was initiated at 300 mg twice daily and titrated to 900 mg three times daily. Initially, Ms. A experienced sedation; this subsided over several weeks. She reported improvement in duration and quality of sleep and energy and significant decreases in irritability, mood lability, and depression. After 3 months of treatment, the patient returned to work for the first time in many years. After 5 months of treatment she continued with marked improvement. Her GAF score increased from a baseline score of 60 to 85, supporting a significant improvement in daily functioning. Case 2. Mr. B., a 49 year old male ([ 8) with
J. Knoll et al. / Journal of Affective Disorders 49 (1998) 229 – 233
231
Table 1 Clinical characteristics and response to gabapentin Patient
1
Age
52
Sex
F
Diagnosis Psychiatric
Medical
BP I, depressed
Bronchitis Hypothyroidism
MV prolapse Migraines
Peak dose
Concomitant
Duration
Gabapentin (mg/day)
Medications (mg/day)
(weeks)
900
2
30
F
BP I, depressed
2400
3
35
F
2400
4
39
F
BP I, mixed Polysubstance abuse, in remission SABP Alcohol abuse, in remission
5
44
F
2700
6
38
F
BP I, Mixed Substance dependence, in remission BP II
7
37
M
BP I
2700
8
49
M
BP I
1800
9
36
F
10
44
F
BP I Panic disorder without agorophobia BP I, depressed
11
48
F
BP I, depressed
12
51
F
BP I, depressed
2400
1800
Hypothyroidism
3300
900 2400
Hypothyroidism
2100
Sertraline 50 Clozapine 250 Thyroxine 0.1 Valproate 750 Lithium 900 Clozapine 50 Bupropion 200 Trifluoperazine 4 Zolpidem 10 Paroxetine 20 Lorazepam 1–2 Perphenazine 48 Amantadine 300 Valproate 1000 Clozapine 325 Clonazepam 2 Fluoxetine 20 Valproate 1000 Lithium 1500 Fluoxetine 20 Diazepam 30 Lithium 900 Clozapine 300
Response
Adverse effects
3
None
Sedation Tremor
8
Moderate
Alopecia
40
Moderate
Nausea
52
Moderate
Fatigue
60
Marked
Sedation
32
Moderate
Weight gain
4
None
Sedation
2
Mild
Sedation Tremor Irritability Irritability
Lithium 900 Thyroxine 0.1
28
Moderate
Valproate 1000 Paroxetine 20 Valproate 1500 Paroxetine 20 Thioridazine 200 Thyroxine 0.25 Lithium 1200 Imipramine 200 Thorazine 125 Propranolol 40 Synthroid.025
36
Moderate
30
Mild
40
Moderate
Sedation Irritability Tremor Fatigue
None
BP I 5 bipolar I disorder; BP II 5 bipolar II disorder; MV5 mitral valve; SABP 5 schizoaffective.
bipolar disorder I, had only partial responses to lithium and carbamazepine. Upon initiation of gabapentin, the patient was receiving clozapine 300 mg and lithium 900 mg daily. Gabapentin was started at 300 mg three times daily. After 7 days the patient reported improvements in sleep and irritability. At this point, the patient’s response was evaluated as moderate. However, there were continued symp-
toms of hypersexuality, grandiosity, and pressured speech. The dose was increased to 600 mg three times daily. The patient reported adverse effects of sedation, increased irritability, and tremors that caused the patient to drop things. Gabapentin was discontinued after 13 days, with a starting and finishing GAF of 40. All adverse effects diminished within 3 days of discontinuation of gabapentin.
232
J. Knoll et al. / Journal of Affective Disorders 49 (1998) 229 – 233
Because of continuation of some manic symptoms, and a return to his lower level of daily functioning, his overall response was evaluated as mild.
4. Discussion The patients in our sample all had severe and persistent affective illness that had failed to respond to traditional mood stabilizing agents. All patients had been ill for more than 10 years. Each had failed trials of the usual mood stabilizers, and continued to have significant symptoms of their illness despite aggressive treatment – including the use of clozapine. Gabapentin yielded moderate responses in the majority of the cases. The primary symptoms improved by gabapentin were mood lability, poor concentration and distractibility, irritability, and variable energy levels. Given the severity of these patients’ illness, a moderate response must be considered a relative success. All patients were taking concomitant medications, so it is unclear how less severely ill patients would respond to gabapentin monotherapy. Half of the sample chose to discontinue due to adverse effects (usually, sedation). Sedation was the most significant and problematic adverse effect encountered in our study. However, although three of the five patients who discontinued gabapentin because of sedation did so early in the trial, two patients continued for many months, making it difficult to attribute their desire to stop to the medication and / or its adverse effects. In contrast, during preclinical trials of gabapentin in patients with epilepsy, 7% of 2074 patients discontinued due to adverse effects, 1.3% because of somnolence (Physicians’ Desk Reference, 1997). One possible explanation for this discrepancy is that patients with epilepsy may be more willing to tolerate adverse effects in exchange for improved seizure control, or that bipolar patients may be more sensitive to this adverse effect. Additionally, all patients in the trial received concomitant medication which may have contributed to sedative side effects. Large clinical trials, currently underway, will provide further information on this issue. The mechanism of action of gabapentin is un-
known. In rats, it appears to bind to neuronal cell bodies in outer layers of cortex and the hippocampus. The distribution of binding is similar to that of glutamate synapses (Taylor, 1994; Hill et al., 1993; Suman-Chauhan et al., 1993). Its putative actions as a mood stabilizer are unclear, though it has been suggested that mood stabilizing AEDs exert their effects via second messenger systems (Stoll and Severus, 1996). In conclusion, gabapentin is associated with moderate improvement of mood symptoms in psychiatric patients. Unlike many other AEDs, blood-level monitoring is unnecessary. Gabapentin is renally eliminated and is associated with few drug–drug interactions. These attributes may be of particular importance in patients who need multiple agents for treatment of their disease. Controlled studies of gabapentin for the treatment of psychiatric disorders are needed to clarify its role in this patient population. Such studies currently are underway.
Acknowledgements Thanks to the Theodore and Vada Stanley Foundation Bipolar Network, a program of the NAMI Research Institute.
References Bennett, J., Goldman, W.T., Suppes, T., 1997. Gabapentin for treatment of bipolar and schizoaffective disorders [letter]. J. Clin. Psychopharmacol. 17 (2), 141–142. Guy, W., 1976. ECDEU Assessment Manual for Psychopharmacology. US Department of Health, Education, and Welfare, Washington DC. Hill, D.R., Suman-Chauhan, N., Woodruff, G.N., 1993. Localization of [ 3 H] gabapentin to a novel site in rat brain: Auto radiographic studies. Eur. J. Pharmacol. Mol. Pharmacol. 244, 303–309. McLean, M.J., 1994. Clinical pharmacokinetics of gabapentin. Neurology 44 (6 Suppl 5), S17–S22. Physicians’ Desk Reference, 1997. Medical Economics, Montvale NJ. Radulovic, L.L., Wilder, B.J., Leppik, I.E. et al., 1994. Lack of interaction of gabapentin with carbamazepine or valproate. Epilepsia 35, 155–161. Ryback, R., Ryback, L., 1995. Gabapentin for behavioral dyscontrol [letter]. Am. J. Psychiatry 152, 1399.
J. Knoll et al. / Journal of Affective Disorders 49 (1998) 229 – 233 Short, C., Cooke, L., 1995. Hypomania induced by gabapentin [letter]. Br. J. Psychiatry 166, 679–680. Stoll, A.L., Severus, W.E., 1996. Mood stabilizers: Shared mechanisms of action at postsynaptic signal-transduction and kindling processes. Harv. Rev. Psychiatry 4, 77–89. Suman-Chauhan, N., Webdale, L., Hill, D.R., Woodruff, G.N.,
233
1993. Characterization of [ 3 H] gabapentin binding to a novel site in rat brain: Homogenate binding studies. Eur. J. Pharmacol. Mol. Pharmacol. 244, 293–301. Taylor, C.P., 1994. Emerging perspectives on the mechanism of action of gabapentin. Neurology 44 (6 Suppl 5), S10–S16.
Preliminary communication
Clinical experience using gabapentin adjunctively in patients with a history of mania or hypomania James Knoll, Kristine Stegman, Trisha Suppes* University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA Received 9 September 1997; accepted 2 October 1997
Abstract Background: Gabapentin is an anticonvulsant proposed to have mood-stabilizing properties. It has been effective in the add-on treatment of refractory partial seizures and secondary generalized tonic–clonic seizures. It has the advantage of a favorable side effect profile and lack of drug interactions. Methods: Twelve consecutive outpatients with persistent, treatment-resistant bipolar spectrum disorders were treated with gabapentin in combination with other medications. Patients were started at 300 mg / day, which was titrated according to clinical response. Response was assessed every 3–4 weeks with a Clinical Global Improvement Scale. Dosage and side effects were noted. The median peak dose was 2400 mg / day. Results: One patient had a marked response to gabapentin; seven, a moderate response; two, mild; and two, no response to treatment. Six patients discontinued treatment due to somatic complaints (i.e., sedation or fatigue). The most frequently reported adverse effect was sedation. Limitations: Gabapentin was added openly, and rating was nonblind in this case series. The use of concomitant medications could have increased the amount of sedation experienced with gabapentin. Conclusion: Overall, gabapentin was associated with moderate improvement of mood symptoms. Given the severity and chronicity of these patients’ illness, a moderate response must be considered a relative success. Controlled studies of gabapentin are needed to clarify its role in the treatment of bipolar disorder. 1998 Elsevier Science B.V. Keywords: Bipolar disorder; Treatment; Anticonvulsants; Mood lability; Gabapentin
1. Introduction The utility of antiepileptic drugs (AEDs) in treating bipolar disorder is an area of intensive study. Gabapentin is a newer AED effective for refractory partial seizures and secondary generalized tonic– clonic seizures. Among the advantages of this drug *Corresponding author. Tel.: 1 1 214 6484211; fax: 1 1 214 6484278.
are a favorable side effect profile and a lack of drug interactions with other AEDs (McLean, 1994; Radulovic et al., 1994). Gabapentin was synthesized to be a g-amino butyric acid (GABA) structural analog; however, no direct effects on GABA pharmacology have been shown (McLean, 1994). Its pharmacokinetics are unique in that it is rapidly absorbed, not protein bound, and is eliminated unmetabolized in the urine (McLean, 1994).
0165-0327 / 98 / $19.00 1998 Elsevier Science B.V. All rights reserved. PII S0165-0327( 98 )00027-5
230
J. Knoll et al. / Journal of Affective Disorders 49 (1998) 229 – 233
There currently are limited data on the psychiatric effects of gabapentin. One case report (Ryback and Ryback, 1995) suggests that gabapentin may be useful for the treatment of behavioral dyscontrol. Bennett et al. (1997) report antimanic efficacy in inpatients with bipolar disorder; however, Short and Cooke (1995) report hypomanic symptoms that may have been induced by gabapentin. This case series reports our clinical experience with gabapentin in 12 consecutive symptomatic patients with a history of mania or hypomania.
tioning (GAF) scale, as outlined in DSM-IV. A mild response generally indicated little or no improvement was seen, and GAF score increase of less than 10 points. A moderate response was generally associated with a 10–20 point improvement, and a marked response was greater than a 20 point improvement. The determination of treatment response was made when each patient had been stabilized at his or her maximal effective dose. Peak dose, total duration of treatment, and adverse effects were recorded.
3. Results 2. Methods Twelve outpatients with persistent, disabling symptoms of mania or hypomania and exhibiting treatment resistance to therapeutic levels of standard mood stabilizers, treatment intolerance, or both, were treated with gabapentin. The mean age of the patients was 42 years (range 30–52). Ten patients were women. All had chronic psychiatric illness, including bipolar I disorder (n 5 10), bipolar II disorder (n 5 1), and schizoaffective, bipolar type (n 5 1). Due to the treatment resistant, chronically ill nature of these patients, most were on concomitant psychotropic agents. Patients were given a starting dose of 300 mg per day and titrated according to clinical response. Individual titration schedules varied, depending upon the patient’s response and tolerance to the drug. Response to gabapentin was assessed every 3–4 weeks with a Clinical Global Improvement Scale (CGI). Each patient was assessed by the same physician at all visits. Treatment response was described as marked, moderate, mild, or no response. At the patients’ first visit, they were given an initial score according to the CGI. A score of 2–3 indicates mild illness, a score of 4–5 indicates moderate illness, and a score of 6–7 indicates marked illness. Throughout the study, patients were evaluated with CGI Improvement Scale, where a score of 1–2 indicated marked improvement, a score of 3 indicated moderate improvement, a score of 4 indicated mild improvement, and a score of 5 or greater indicated no improvement (Guy, 1976). Throughout the study, patients’ clinical progress was also evaluated using the 0–100 Global Assessment of Func-
Treatment duration ranged 3–60 weeks and peak dosages ranged 900–3300 mg / day (median dose 5 2400 mg / day). Titration schedules varied due to differences in patient tolerance. One patient had a marked response to gabapentin, during which manic symptoms and CGI were significantly improved (Table 1). Seven patients had moderate responses, two had mild responses, and two had no response to treatment. Treatment was discontinued in seven patients. Patient [ 2 developed mild alopecia and patient [ 3 dropped out due to a possible pregnancy. Seven (58%) patients reported sedation or fatigue, and five (42%) chose to discontinue treatment as a result of these adverse effects ([ 1, 7, 8, 10, 11). The following cases describe one patient with a marked response and another with a mild response: Case 1. Ms. A, a 44 year old woman ([5) with bipolar disorder I, mixed episode, previously failed a trial of combined valproate and lithium therapy. When gabapentin was initiated, the patient was on a regimen of clozapine 325 mg, valproate 1000 mg, and clonazepam 2 mg daily. Gabapentin was initiated at 300 mg twice daily and titrated to 900 mg three times daily. Initially, Ms. A experienced sedation; this subsided over several weeks. She reported improvement in duration and quality of sleep and energy and significant decreases in irritability, mood lability, and depression. After 3 months of treatment, the patient returned to work for the first time in many years. After 5 months of treatment she continued with marked improvement. Her GAF score increased from a baseline score of 60 to 85, supporting a significant improvement in daily functioning. Case 2. Mr. B., a 49 year old male ([ 8) with
J. Knoll et al. / Journal of Affective Disorders 49 (1998) 229 – 233
231
Table 1 Clinical characteristics and response to gabapentin Patient
1
Age
52
Sex
F
Diagnosis Psychiatric
Medical
BP I, depressed
Bronchitis Hypothyroidism
MV prolapse Migraines
Peak dose
Concomitant
Duration
Gabapentin (mg/day)
Medications (mg/day)
(weeks)
900
2
30
F
BP I, depressed
2400
3
35
F
2400
4
39
F
BP I, mixed Polysubstance abuse, in remission SABP Alcohol abuse, in remission
5
44
F
2700
6
38
F
BP I, Mixed Substance dependence, in remission BP II
7
37
M
BP I
2700
8
49
M
BP I
1800
9
36
F
10
44
F
BP I Panic disorder without agorophobia BP I, depressed
11
48
F
BP I, depressed
12
51
F
BP I, depressed
2400
1800
Hypothyroidism
3300
900 2400
Hypothyroidism
2100
Sertraline 50 Clozapine 250 Thyroxine 0.1 Valproate 750 Lithium 900 Clozapine 50 Bupropion 200 Trifluoperazine 4 Zolpidem 10 Paroxetine 20 Lorazepam 1–2 Perphenazine 48 Amantadine 300 Valproate 1000 Clozapine 325 Clonazepam 2 Fluoxetine 20 Valproate 1000 Lithium 1500 Fluoxetine 20 Diazepam 30 Lithium 900 Clozapine 300
Response
Adverse effects
3
None
Sedation Tremor
8
Moderate
Alopecia
40
Moderate
Nausea
52
Moderate
Fatigue
60
Marked
Sedation
32
Moderate
Weight gain
4
None
Sedation
2
Mild
Sedation Tremor Irritability Irritability
Lithium 900 Thyroxine 0.1
28
Moderate
Valproate 1000 Paroxetine 20 Valproate 1500 Paroxetine 20 Thioridazine 200 Thyroxine 0.25 Lithium 1200 Imipramine 200 Thorazine 125 Propranolol 40 Synthroid.025
36
Moderate
30
Mild
40
Moderate
Sedation Irritability Tremor Fatigue
None
BP I 5 bipolar I disorder; BP II 5 bipolar II disorder; MV5 mitral valve; SABP 5 schizoaffective.
bipolar disorder I, had only partial responses to lithium and carbamazepine. Upon initiation of gabapentin, the patient was receiving clozapine 300 mg and lithium 900 mg daily. Gabapentin was started at 300 mg three times daily. After 7 days the patient reported improvements in sleep and irritability. At this point, the patient’s response was evaluated as moderate. However, there were continued symp-
toms of hypersexuality, grandiosity, and pressured speech. The dose was increased to 600 mg three times daily. The patient reported adverse effects of sedation, increased irritability, and tremors that caused the patient to drop things. Gabapentin was discontinued after 13 days, with a starting and finishing GAF of 40. All adverse effects diminished within 3 days of discontinuation of gabapentin.
232
J. Knoll et al. / Journal of Affective Disorders 49 (1998) 229 – 233
Because of continuation of some manic symptoms, and a return to his lower level of daily functioning, his overall response was evaluated as mild.
4. Discussion The patients in our sample all had severe and persistent affective illness that had failed to respond to traditional mood stabilizing agents. All patients had been ill for more than 10 years. Each had failed trials of the usual mood stabilizers, and continued to have significant symptoms of their illness despite aggressive treatment – including the use of clozapine. Gabapentin yielded moderate responses in the majority of the cases. The primary symptoms improved by gabapentin were mood lability, poor concentration and distractibility, irritability, and variable energy levels. Given the severity of these patients’ illness, a moderate response must be considered a relative success. All patients were taking concomitant medications, so it is unclear how less severely ill patients would respond to gabapentin monotherapy. Half of the sample chose to discontinue due to adverse effects (usually, sedation). Sedation was the most significant and problematic adverse effect encountered in our study. However, although three of the five patients who discontinued gabapentin because of sedation did so early in the trial, two patients continued for many months, making it difficult to attribute their desire to stop to the medication and / or its adverse effects. In contrast, during preclinical trials of gabapentin in patients with epilepsy, 7% of 2074 patients discontinued due to adverse effects, 1.3% because of somnolence (Physicians’ Desk Reference, 1997). One possible explanation for this discrepancy is that patients with epilepsy may be more willing to tolerate adverse effects in exchange for improved seizure control, or that bipolar patients may be more sensitive to this adverse effect. Additionally, all patients in the trial received concomitant medication which may have contributed to sedative side effects. Large clinical trials, currently underway, will provide further information on this issue. The mechanism of action of gabapentin is un-
known. In rats, it appears to bind to neuronal cell bodies in outer layers of cortex and the hippocampus. The distribution of binding is similar to that of glutamate synapses (Taylor, 1994; Hill et al., 1993; Suman-Chauhan et al., 1993). Its putative actions as a mood stabilizer are unclear, though it has been suggested that mood stabilizing AEDs exert their effects via second messenger systems (Stoll and Severus, 1996). In conclusion, gabapentin is associated with moderate improvement of mood symptoms in psychiatric patients. Unlike many other AEDs, blood-level monitoring is unnecessary. Gabapentin is renally eliminated and is associated with few drug–drug interactions. These attributes may be of particular importance in patients who need multiple agents for treatment of their disease. Controlled studies of gabapentin for the treatment of psychiatric disorders are needed to clarify its role in this patient population. Such studies currently are underway.
Acknowledgements Thanks to the Theodore and Vada Stanley Foundation Bipolar Network, a program of the NAMI Research Institute.
References Bennett, J., Goldman, W.T., Suppes, T., 1997. Gabapentin for treatment of bipolar and schizoaffective disorders [letter]. J. Clin. Psychopharmacol. 17 (2), 141–142. Guy, W., 1976. ECDEU Assessment Manual for Psychopharmacology. US Department of Health, Education, and Welfare, Washington DC. Hill, D.R., Suman-Chauhan, N., Woodruff, G.N., 1993. Localization of [ 3 H] gabapentin to a novel site in rat brain: Auto radiographic studies. Eur. J. Pharmacol. Mol. Pharmacol. 244, 303–309. McLean, M.J., 1994. Clinical pharmacokinetics of gabapentin. Neurology 44 (6 Suppl 5), S17–S22. Physicians’ Desk Reference, 1997. Medical Economics, Montvale NJ. Radulovic, L.L., Wilder, B.J., Leppik, I.E. et al., 1994. Lack of interaction of gabapentin with carbamazepine or valproate. Epilepsia 35, 155–161. Ryback, R., Ryback, L., 1995. Gabapentin for behavioral dyscontrol [letter]. Am. J. Psychiatry 152, 1399.
J. Knoll et al. / Journal of Affective Disorders 49 (1998) 229 – 233 Short, C., Cooke, L., 1995. Hypomania induced by gabapentin [letter]. Br. J. Psychiatry 166, 679–680. Stoll, A.L., Severus, W.E., 1996. Mood stabilizers: Shared mechanisms of action at postsynaptic signal-transduction and kindling processes. Harv. Rev. Psychiatry 4, 77–89. Suman-Chauhan, N., Webdale, L., Hill, D.R., Woodruff, G.N.,
233
1993. Characterization of [ 3 H] gabapentin binding to a novel site in rat brain: Homogenate binding studies. Eur. J. Pharmacol. Mol. Pharmacol. 244, 293–301. Taylor, C.P., 1994. Emerging perspectives on the mechanism of action of gabapentin. Neurology 44 (6 Suppl 5), S10–S16.