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Lamotrigina para la esquizofrenia

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Referencias

Referencias de los estudios incluidos en esta revisión

Ir a:

Akhondzadeh 2005 {published data only}

Akhondzadeh S, Mackinejad K, Ahmadi‐Abhari SA, Alem ZM. Does the addition of lamotrigine to risperidone improve psychotic symptoms and cognitive impairments in chronic schizophrenia?. Therapy 2005;2(3):399‐406. [ISSN 0308‐7808]

Goff 2006a {published data only}

Goff D, Keefe R, Volavka J, Krystal J, Davy K, Thompson T, Webster E. Lamotrigine Added to Atypical Antipsychotics for Treatment of Schizophrenia: Results of Two Double‐Blind Randomized Clinical Trials. American Psychiatric Association Annual Meeting. 2006.
Goff DC, GlaxoSmithKline. A multi‐center, double blind, placebo controlled, randomized, parallel group evaluation of the efficacy of a flexible dose of lamotrigine versus placebo as add‐on therapy in schizophrenia. GlaxoSmithKline Clinical Trial Register2006. [MEDLINE: Clinical trials.gov NCT00071747; CSG No: 9009]

Goff 2006b {published data only}

Goff D, Keefe R, Volavka J, Krystal J, Davy K, Thompson T, Webster E. Lamotrigine Added to Atypical Antipsychotics for Treatment of Schizophrenia: Results of Two Double‐Blind Randomized Clinical Trials. American Psychiatric Association Annual Meeting. 2006.
Goff DC, GlaxoSmithKline. A multicenter, randomised, double‐blind, parallel group study to evaluate the efficacy and safety of a flexible dose of lamotrigine compared to placebo as an adjunctive therapy to an atypical antipsychotic agent(s) in subjects with schizophrenia.. GlaxoSmithKline Clinical Trial Register2006. [MEDLINE: Clinicaltrials.gov NCT00086593; CSG No: 9010]

Kremer 2004 {published data only}

Kremer I, Vass A, Gorelik I, Bar G, Blanaru M, Javitt DC, Heresco‐Levy U. Placebo‐controlled trial of lamotrigine added to conventional and atypical antipsychotics in schizophrenia. Biological Psychiatry 2004;56(6):441‐6. [EMBASE 2004385406]
Vass A, Kremer I, Gurelik I, Blenaru M, Bar G, Javitt D, Heresco‐Levy U. Pilot‐controlled trial of lamotrigine adjuvant treatment in schizophrenia. 157th Annual Meeting of the American Psychiatric Association; 2004 May 1‐6; New York, New York, USA. 2004. [APA Conference Abstracts NR395]

Tiihonen 2003 {published data only}

Tiihonen J, Hallikainen T, Ryynänen O‐P, Repo‐Tiihonen E, Kotilainen I, Eronen M, Toivonen P, Wahlbeck K, Putkonen A. Lamotrigine in clozapine treatment‐resistant schizophrenia [Lamotrigiini klotsapiiniresistentissa skitsofreniassa]. Duodecim 2004;120(1):85‐6. [MEDLINE:  14976813; CN‐00467466.]
Tiihonen J, Hallikainen T, Ryynänen O‐P, Repo‐Tiihonen E, Kotilainen I, Eronen M, Toivonen P, Wahlbeck K, Putkonen A. Lamotrigine in clozapine‐resistant schizophrenia: A randomized placebo‐controlled cross‐over trial. Journal of the European College of Neuropsychopharmacology 2002;12(Suppl 3):S262. [Hallo P.2.019]
Tiihonen J, Hallikainen T, Ryynänen O‐P, Repo‐Tiihonen E, Kotilainen I, Eronen M, Toivonen P, Wahlbeck K, Putkonen A. Lamotrigine in treatment‐resistant schizophrenia. A randomized, placebo‐controlled, trial. Nordic Journal of Psychiatry 2002;56(2):30.
Tiihonen J, Hallikainen T, Ryynänen O‐P, Repo‐Tiihonen E, Kotilainen IEM, Toivonen P, Wahlbeck K, Putkonen A. Lamotrigine in treatment‐resistant schizophrenia: a randomized placebo‐controlled crossover trial. Biological Psychiatry 2003;54(11):1241‐8. [MEDLINE: 14643092]
Tilhonen J, Wahlbeck K. A randomized, placebo‐controlled, crossover trial of lamotrigine augmentation of clozapine, risperidone, and olanzapine in 50 in‐patients with treatment‐resistant schizophrenia. Stanley Foundation Research Programs2002.

Referencias de los estudios excluidos de esta revisión

Ir a:

Anand 1999 {published data only}

Anand A, Berman R, Oren D, Charney DS, Krystal JH. Attenuation of nmda antagonist effects in healthy humans by lamotrigine, a drug that reduces glutamate release. Schizophrenia Research 1999;1,2 & 3:305.
Anand A, Charney DS, Oren DA, Berman RM, Hu XS, Cappiello A, Krystal JH. Attenuation of the neuropsychiatric effects of ketamine with lamotrigine: support for hyperglutamatergic effects of N‐methyl‐D‐aspartate receptor antagonists. Archives of General Psychiatry 2000;57(3):270‐6. [MEDLINE: 10711913; PsycINFO 2000‐03078‐008]

Bowden 2000 {published data only}

Bowden C. Mood stabilisers for rapid‐cycling bipolar disorder. Stanley Foundation Research Programs2000.

Calabrese 2000 {published data only}

Calabrese J, et al. Mood stabilisers for rapid‐cycling bipolar disorder. Stanley Foundation Research Programs2000.

Heck 2005 {published data only}

Heck AH, De Groot IW, Van Harten PN. Addition of lamotrigine to clozapine in inpatients with chronic psychosis. Journal of Clinical Psychiatry 2005;66(10):1333. [EMBASE: 2005490713]

Kolivakis 2001 {published data only}

Kolivakis TT, Margolese HC, Beauclair L, Chouinard G. Adjunctive anticonvulsant use in first‐episode schizophrenia. 154th Annual Meeting of the American Psychiatric Association; 2001 May 5‐10; New Orleans, Louisiana, USA. Marathon Multimedia, 2001.

Kolivakis 2002 {published data only}

Kolivakis TT, Margolese HC, Beauclair L, Chouinard G. Adjunctive anticonvulsant use in first‐episode schizophrenia. 155th Annual Meeting of the American Psychiatric Association; 2002 May 18‐23; Philadelphia, Pennsylvania, USA. 2002. [NR302 Tuesday, May 8, 12:00 p.m.‐2:00 pm]

Kolivakis 2004 {published data only}

Kolivakis TT, Beauclair L, Margolese HC, Chouinard G. Long‐Term lamotrigine adjunctive to antipsychotic monotherapy in schizophrenia: further evidence Adjunctive to Antipsychotic Monotherapy in Schizophrenia: Further Evidence. Canadian Journal of Psychiatry 2004;49(4):280.

Sikich 2004 {published data only}

Sikich L, Hamer RM, Bashford RA, Sheitman BB, Lieberman JA. A pilot study of risperidone, olanzapine, and haloperidol in psychotic youth: a double‐blind, randomized, 8‐week trial. Neuropsychopharmacology 2004;29(1):133‐45. [MEDLINE: 14583740; EMBASE: 2004025276]

Woods 2002 {published data only}

Woods SW, Wexler BE, Miller TJ, Hawkins KA, Saab WA, Davidson L, McGlashan TH. Novel early interventions for prodromal states. 155th Annual Meeting of the American Psychiatric Association; 2002 May 18‐23; Philadelphia, Pennsylvania, USA. 2002. [No. 58E]

Referencias de los estudios en espera de evaluación

Ir a:

Adityanjee 2000 {published data only}

Adityanjee CJ. Lamotrigine for schizophrenia. Stanley Foundation Research Programs2000.

Bustillo 2001 {published data only (unpublished sought but not used)}

Bustillo J. Summaries of approved treatment trial grants from the March 2001 submissions. Stanley Medical Research Institute2001.

Addington 1990

Addington D, Addington J, Schissel, B. A depression rating scale for schizophrenics. Schizophrenia Research 1997;3:247‐251.

Altman 1996

Altman DG, Bland JM. Detecting skewness from summary information. BMJ 1996;313(7066):1200.

Andreasen 1983

Andreasen NC. Negative symptoms in schizophrenia. Archives of General Psychiatry 1982;39:784‐8.

APA 1994

American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders (DSM‐IV). 4th Edition. Washington, DC: American Psychiatric Association, 1994.

Bland 1997

Bland JM. Statistics notes. Trials randomised in clusters. BMJ 1997;315:600.

Botts 1999

Botts SR, Raskind J. Gabapentin and lamotrigine in bipolar disorder. American Journal of Health System Pharmacy 1999;56(19):1939‐44.

Bowden 1996

Bowden CL. Role of newer medications for bipolar disorder. Journal of Clinical Psychopharmacology 1996;16(2 Suppl 1):48‐55.

Calabrese 1999

Calabrese JR, Bowden CL, Sachs GS, et al. A double‐blind placebo controlled study of lamotrigine monotherapy in out‐patients with bipolar 1 depression. Lamictal 602 Study Group. Journal of Clinical Psychiatry 1999;60(2):79‐88.

Chouinard 1980

Chouinard G, Ross‐Chouinard A, Annable L. Extrapyramidal symptom rating scale. Canadian Journal of Neurological Science 1980;7:233.

Conley 1997

Conley RR, Buchanan RW. Evaluation of treatment resistant schizophrenia. Schizophrenia Bulletin 1997;23(4):663‐74.

Divine 1992

Divine GW, Brown JT, Frazier LM. The unit of analysis error in studies about physicians' patient care behavior. Journal of General Internal Medicine 1992;7(6):623‐9.

Donner 2002

Donner A, Klar N. Issues in the meta‐analysis of cluster randomized trials. Statistics in Medicine 2002;21:2971‐80.

Ferrier 1998

Ferrier IN. Lamotrigine and Gabapentin‐alternatives in the treatment of bipolar disorder. Neuropsychobiology 1998;38(3):192‐7.

Frances 1996

Frances A, Docherty JP, Kahn DA. The expert consensus guidelines series: Treatment of Schizophrenia. Journal of Clinical Psychiatry 1996;57(12):11‐50.

Golden 1978

Golden CJ. Stroop color and word test. Manual for Clinical and Experimental uses. Stoelting, IL, USA, 30150, 1978.

Gulliford 1999

Gulliford MC. Components of variance and intraclass correlations for the design of community‐based surveys and intervention studies: data from the Health Survey for England 1994. American Journal of Epidemiology 1999;149:876‐83 876‐83.

Guy 1976

Guy W. Early clinical drug evaluation (ECDEU) assessment manual for psychopharmacology. Washington, DC: National Institute of Mental Health, 1976:217‐22. [Publication No.76‐338.]

Hamilton 1960

Hamilton M. A rating scale of depression. Journal of Neurology, Neurosurgery and Psychiatry 1960;23:56‐62.

Herz 1997

Herz MK, Liberman RP, Lieberman JA, et al. American Psychiatric Association practice guideline for the treatment of patients with schizophrenia. American Journal of Psychiatry 1997;154(Suppl 4):1–63.

Higgins 2003

Higgins JPT, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta‐analyses. BMJ 2003;327:557‐60.

Higgins 2005

Higgins JPT, Green S, editors. Cochrane Handbook for Systematic Reviews of Interventions 4.2.5 [updated May 2005]. In: The Cochrane Library. Issue 3, 2005. Chichester, UK:: John Wiley & Sons, Ltd, 2005.

Häfner 1997

Häfner H, Heiden W. Epidemiology of Schizophrenia. Canadian Journal of Psychiatry 1997;42:139‐151.

Jadad 1996

Jadad A, Moore A, Carroll D, Jenkinson C, Reynolds DJM, Gavaghan DJ, McQuay HJ. Assessing the quality of reports of randomized clinical trials: is blinding necessary?. Controlled Clinical Trials 1996;17:1‐12.

Jüni 2001

Jüni P, Altman DG, Egger M. Systematic reviews in health care: Assessing the quality of controlled clinical trials. BMJ 2001;323:42‐6.

Kane 1988

Kane J.M, Honigfield G, Singer J. Clozapine for the treatment resistant schizophrenic: a double blind comparison versus chlorpromazine/ benztropine. Archives of General Psychiatry 1988;45:789‐96.

Kay 1986

Kay SR, Opler LA, Fiszbein A. Positive and negative syndrome scale (PANSS) manual. North Tonawanda, NY: Multi‐Health Systems, 1986.

Keefe 2004

Keefe, R. S. E, Goldberg, T. E, Harvey, P. D, Gold, J. M, Poe, M, & Coughenour, L. The Brief Assessment of Cognition in Schizophrenia: Reliability, sensitivity, and comparison with a standard neurocognitive battery. Schizophrenia Research 2004;68(2‐3):283‐297.

Large 2005

Large CH, Webster EL, Goff DC. The potential role of lamotrigine in schizophrenia. Psychopharmacology 2005;181(3):415‐36.

Leach 1986

Leach MJ, Marsden CM, Miller AA. Pharmacological studies on lamotrigine, a novel potential antiepileptic drug: ii. Neurochemical studies on the mechanism of action. Epilepsia 1986;27(5):490‐7.

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Lehmann H E, Ban T A. The History of the Psychopharmacology of Schizophrenia. Canadian Journal of Psychiatry 1997;42:152‐62.

Leucht 2003

Leucht S, Wahlbeck K, Hamann J, et al. New generation antipsychotics versus low‐potency conventional antipsychotics: a systematic review and meta‐analysis. Lancet 2003;361:1581–89.

Leucht 2005

Leucht S, Kane JM, Kissling W, Hamann J, Etschel E, Engel RR. What does the PANSS mean?. Schizophrenia Research 2005;79:231‐38.

Mackay 1997

Mackay FJ, Wilton LV, Pearce GL, et al. Safety of long term lamotrigine in epilepsy. Epilepsia 1997;38(8):881‐886.

Marshall 2000

Marshall M, Lockwood A, Bradley C, Adams C, Joy C, Fenton M. Unpublished rating scales: a major source of bias in randomised controlled trials of treatments for schizophrenia. British Journal of Psychiatry 2000;176:249‐52.

Moher 2001

Moher D, Schulz KF, Altman D. The CONSORT statement: revised recommendations for improving the quality of reports of parallel‐group randomized trials. JAMA 2001;285:1987‐91.

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Overall JE, Gorham DR. The Brief Psychiatric Rating Scale. Psychological Reports 1962;10:799‐812.

Pantelis 1996

Pantelis C, Barnes TRE. Drug strategies and treatment‐resistant schizophrenia. Australian and New Zealand Journal of Psychiatry 1996;30:20‐37.

Stahl 2004

Stahl SM. Anticonvulsants as mood stabilizers and adjuncts to antipsychotics: valproate, lamotrigine, carbamazepine, and oxcarbazepine and actions at voltage‐gated sodium channels. Journal of Clinical Psychiatry 2004;65(6):738‐9.

Thomas 2005

Thomas R, Howe V, Foister K. Adjunctive lamotrigine in treatment‐resistant schizophrenia. International Journal of Neuropsychopharmacology 2005;Jul(8):1‐3.

Ukoumunne 1999

Ukoumunne OC, Gulliford MC, Chinn S, Sterne JAC, Burney PGJ. Methods for evaluating area‐wide and organistation‐based intervention in health and health care: a systematic review. Health Technology Assessment 1999;3(5):1‐75.

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Ware JE, Sherbourne CD. The MOS 36‐Item Short‐Form Health Survey (SF‐36). Medical Care 1992;30:473‐483.

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World Health Organization: Regional Office for Europe. Well‐ Being measures in primary health care: The DepCare Project. Consensus meeting. Stockholm, 1988.

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World Health Organization. The tenth revision of the International Classification of Diseases and related health problems (ICD‐10). 10th Edition. Geneva: World Health Organization, 1992.

Characteristics of studies

Characteristics of included studies [ordered by study ID]

Ir a:

Akhondzadeh 2005

Methods

Allocation: randomised in 1:1 ratio, computer generated code.
Blinding: double.
Duration: 8 weeks.
Design: single centre, Iran.

Participants

Diagnosis: schizophrenia (DSM IV).
N=36.
Age: 20‐40 years.
Sex: 19 M, 17 F.
Setting: hospital.
History: minimum score of 60 on PANSS, neuroleptic free period prior to trial.
Exclusion: organic, neurologic disorder, substance abuse, mental retardation, renal or liver impairment, allergy to lamotrigine, pregnant or lactating women, participation in other drug trials.

Interventions

1. Lamotrigine 150 mg/day + risperidone 6 mg. N=18.

2. Placebo + risperidone 6 mg. N=18.

Biperiden, as required to both groups.

Outcomes

Mental state: PANSS (data for total, negative symptoms and general psychopathology subscales approximated from graph).
Leaving the study early.
Cognitive state: Stroop color word test.
Adverse effects: ESRS, frequency of adverse effects, anticholinergic use (skewed data).

Unable to use ‐
Mental state: PANSS positive subscale (unable to extract data in graphic).
Physiological tests (no data).

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear
Goff 2006a

Methods

Allocation: randomised in approximately 1:1 ratio, stratified by current therapy.
Blinding: double, identical tablets.
Duration: 12 weeks.
Design: multicentre 27 centres, USA.

Participants

Diagnosis: schizophrenia, schizoaffective disorder.
N= 217*.
Age: 18‐65 years.
Sex: 147 M, 62 F.
Setting: unclear.
History: prior persistent positive symptoms, regular antipsychotic use prior 3 months, stable dose of antipsychotic for prior 1 month.
Exclusion: change more than 20% from screening to baseline.

Interventions

1. Lamotrigine + other atypical antipsychotic (including clozapine): dose 125 mg/day, flexible dose. N=109.

2. Placebo + other atypical antipsychotic. N=108.

Outcomes

Global effect: CGI‐S (data skewed).
Mental state: CDSS, PANSS, SANS (data skewed).
Cognitive state: BACS (data skewed).
Leaving the study early.
Adverse effects.

Notes

* number randomised, numbers in text and table differ.

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear
Goff 2006b

Methods

Allocation: random ‐ no further details.
Blinding: double, identical tablets.
Duration: 12 weeks.
Design: multicentre 31 centres, USA, Canada, UK.

Participants

Diagnosis: schizophrenia.
N=212.
Age: 18‐65 years.
Sex: 156 M, 56 F.
Setting: unclear.
History: prior persistent positive symptoms, regular antipsychotic use prior 3 months, stable dose of antipsychotic for prior 1 month.
Exclusion: change more than 20% from screening to baseline.

Interventions

1. Lamotrigine + other atypical antipsychotics (including clozapine): dose 200 mg/day up to week 6, flexible blind titration weeks 7‐12. N=106.

2. Placebo + other atypical antipsychotic. N=106.

Outcomes

Global effect: CGI ‐I, CGI‐S, SF‐36, WHO‐5 (data skewed).
Mental state: BACS, CDSS, PANSS, SANS.
Leaving the study early.
Adverse effects.

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear
Kremer 2004

Methods

Allocation: randomised, 2:1 ratio.
Blinding: double, identical capsules.
Duration: 10 weeks (preceded by 2 week non random run‐in).
Design: single centre hospital, Israel.

Participants

Diagnosis: schizophrenia (DSM IV).
N=38.
Age: 30‐55 years.
Sex: 23 M, 15 F.
Setting: hospital.
History: resistance to prior 3 treatment periods, stable dose antipsychotic for prior 2 months.
Exclusions: recent antidepressant, anticonvulsant or ECT use, comorbid DSM IV diagnoses or medical illness.

Interventions

1. Lamotrigine + other antipsychotic (including clozapine): dose up to 400 mg/day, dose built up over 8 weeks; maximum dose held steady only in the last two weeks. N=25.

2. Placebo + other atypical antipsychotic. N=13.

Both groups as required ‐ trihexyphenidyl: 2‐5 mg, chloral hydrate: 250‐750 mg.

Outcomes

Mental state: PANSS, BPRS, SANS, HAM‐D21.
Leaving the study early.

Unable to use ‐
Adverse events (no usable data).
Physiological tests (no usable data).

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Low risk

A ‐ Adequate
Tiihonen 2003

Methods

Allocation: block randomisation by random number generator, stratified by GAF scores, cross over after 14 weeks.
Blinding: double, identical capsules.
Duration: 28 weeks (two 14‐week treatment periods, one week placebo lead‐in).
Design: single centre, Finland.

Participants

Diagnosis: schizophrenia (DSM IV), paranoid, disorganized, undifferentiated, residual.
N=34.
Sex: 34 M.
Age: 18‐60 years.
Setting: hospital.
History: non‐satisfactory response to ongoing clozapine treatment, resistance to prior 2 treatment periods.
Exclusions: present anticonvulsant or lithium use, co‐morbid epilepsy, GAF < 20.

Interventions

1. Lamotrigine + clozapine: dose up to 200 mg/day, tapered in the last week. N=16*.

2. Placebo + clozapine. N=18.

Outcomes

Mental state: PANSS positive subscale (first phase before cross‐over).
Leaving the study early.

Unable to use ‐
Mental state: PANSS total, negative and general psychopathology subscales (cross‐over, first phase results not reported separately).
Adverse effects (values in percentages).
Physiological tests.

Notes

*first phase of trial only, before cross‐over.

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Low risk

A ‐ Adequate

DSM IV ‐ Diagnostic and Statistical Manual of mental disorders. 4th edition
ECT ‐ Electro‐convulsive Therapy
SD ‐ standard deviation

Mental state ‐
BACS ‐ Brief Assessment of Cognition for Schizophrenia (BACS)
BPRS ‐ Brief Psychiatric Rating Scale
CDSS ‐ Calgary Depression Scale for Schizophrenia
HAM‐D21 ‐ 21‐item Hamilton Rating Scale for Depression
PANSS ‐ Positive and Negative Syndrome Scale
SANS ‐ Scale for Assessment of Negative Symptoms

Global state ‐
CGI ‐ I ‐ Clinical Global Impression ‐ Improvement
CGI ‐ S ‐ Clinical Global Impression ‐ Severity
GAF ‐ Global Assessment of Functioning
SF‐36 ‐ Short Form 36
WHO‐5 ‐ World Health Organisation‐5 Well Being Index

Adverse effects ‐
ESRS ‐ Extrapyramidal Symptoms Rating Scale

Characteristics of excluded studies [ordered by study ID]

Ir a:

Study

Reason for exclusion

Anand 1999

Allocation: randomised.
Participants: healthy people, not people with schizophrenia.

Bowden 2000

Allocation: unclear.
Participants: people with rapid cycling bipolar disorder, not people with schizophrenia.

Calabrese 2000

Allocation: unclear.
Participants: people with rapid cycling bipolar disorder, not people with schizophrenia.

Heck 2005

Allocation: not randomised.

Kolivakis 2001

Allocation: randomised.
Participants: people with schizophrenia.
Interventions: risperidone versus haloperidol, not lamotrigine.

Kolivakis 2002

Allocation: randomised.
Participants: people with schizophrenia.
Interventions: risperidone versus haloperidol, not lamotrigine.

Kolivakis 2004

Allocation: open label trial, not a randomised trial.

Sikich 2004

Allocation: randomised.
Participants: people with schizophrenia.
Interventions: risperidone versus olanzapine versus haloperidol, not lamotrigine.

Woods 2002

Allocation: randomised.
Participants: people with schizophrenia.
Interventions: lamotrigine versus placebo.
Outcomes: no usable data, this document was a proposal for a study, never conducted.

Data and analyses

Open in table viewer
Comparison 1. ADJUNCTIVE LAMOTRIGINE vs ADJUNCTIVE PLACEBO

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Global state: 1.Global improvement (CGI‐I) Show forest plot

1

208

Risk Ratio (M‐H, Random, 95% CI)

1.06 [0.73, 1.54]
Analysis 1.1
Comparison 1 ADJUNCTIVE LAMOTRIGINE vs ADJUNCTIVE PLACEBO, Outcome 1 Global state: 1.Global improvement (CGI‐I).

Comparison 1 ADJUNCTIVE LAMOTRIGINE vs ADJUNCTIVE PLACEBO, Outcome 1 Global state: 1.Global improvement (CGI‐I).

2 Global state: 2. Average total change score ‐ short term (CGI‐S, high change=good, data skewed) Show forest plot

Other data

No numeric data
Analysis 1.2

Study

Intervention

Least Mean Square

SD

N

Notes

Goff 2006a

Adjuvant lamotrigine

‐0.2

0.82

101

Goff 2006a

Adjuvant placebo

‐0.5

0.82

104

Goff 2006b

Adjuvant lamotrigine

‐0.5

0.72

104

Goff 2006b

Adjuvant placebo

‐0.4

0.72

104

Comparison 1 ADJUNCTIVE LAMOTRIGINE vs ADJUNCTIVE PLACEBO, Outcome 2 Global state: 2. Average total change score ‐ short term (CGI‐S, high change=good, data skewed).

3 Global state: 3. Average physical health change score ‐ short term (SF‐36, high change=good, data skewed) Show forest plot

Other data

No numeric data
Analysis 1.3

Study

Intervention

Least Square Mean

SD

N

Notes

Goff 2006b

Adjuvant lamotrigine

0.07

7.18

87

Goff 2006b

Adjuvant placebo

‐0.31

7.22

88

Comparison 1 ADJUNCTIVE LAMOTRIGINE vs ADJUNCTIVE PLACEBO, Outcome 3 Global state: 3. Average physical health change score ‐ short term (SF‐36, high change=good, data skewed).

4 Global state: 4. Average mental health change score ‐ short term (SF‐36, high change=good, data skewed) Show forest plot

Other data

No numeric data
Analysis 1.4

Study

Intervention

Least Square Mean

SD

N

Notes

Goff 2006b

Adjuvant lamotrigine

0.21

8.21

87

Goff 2006b

Adjuvant placebo

1.32

8.16

88

Comparison 1 ADJUNCTIVE LAMOTRIGINE vs ADJUNCTIVE PLACEBO, Outcome 4 Global state: 4. Average mental health change score ‐ short term (SF‐36, high change=good, data skewed).

5 Mental state: 1.Treatment responders (> 20% reduction in PANSS total) Show forest plot

3

297

Risk Ratio (M‐H, Random, 95% CI)

1.26 [0.81, 1.97]
Analysis 1.5
Comparison 1 ADJUNCTIVE LAMOTRIGINE vs ADJUNCTIVE PLACEBO, Outcome 5 Mental state: 1.Treatment responders (> 20% reduction in PANSS total).

Comparison 1 ADJUNCTIVE LAMOTRIGINE vs ADJUNCTIVE PLACEBO, Outcome 5 Mental state: 1.Treatment responders (> 20% reduction in PANSS total).

6 Mental state: 2a. Average total endpoint score ‐ short term (PANSS, high=poor) Show forest plot

2

67

Mean Difference (IV, Random, 95% CI)

‐16.88 [‐25.18, ‐8.57]
Analysis 1.6
Comparison 1 ADJUNCTIVE LAMOTRIGINE vs ADJUNCTIVE PLACEBO, Outcome 6 Mental state: 2a. Average total endpoint score ‐ short term (PANSS, high=poor).

Comparison 1 ADJUNCTIVE LAMOTRIGINE vs ADJUNCTIVE PLACEBO, Outcome 6 Mental state: 2a. Average total endpoint score ‐ short term (PANSS, high=poor).

7 Mental state: 2b. Average total endpoint score ‐ short term (BPRS, high=poor) Show forest plot

1

31

Mean Difference (IV, Random, 95% CI)

‐2.80 [‐12.44, 6.84]
Analysis 1.7
Comparison 1 ADJUNCTIVE LAMOTRIGINE vs ADJUNCTIVE PLACEBO, Outcome 7 Mental state: 2b. Average total endpoint score ‐ short term (BPRS, high=poor).

Comparison 1 ADJUNCTIVE LAMOTRIGINE vs ADJUNCTIVE PLACEBO, Outcome 7 Mental state: 2b. Average total endpoint score ‐ short term (BPRS, high=poor).

8 Mental state: 2c. Average total change score ‐ short term (PANSS, high=poor, data skewed) Show forest plot

Other data

No numeric data
Analysis 1.8

Study

Intervention

Least Square Mean

SD

N

Notes

Goff 2006a

Adjuvant lamotrigine

‐6.0

13.77

101

Goff 2006a

Adjuvant placebo

‐8.2

13.84

104

Goff 2006b

Adjuvant lamotrigine

‐12.9

12.34

103

Goff 2006b

Adjuvant placebo

‐12.0

12.40

104

Comparison 1 ADJUNCTIVE LAMOTRIGINE vs ADJUNCTIVE PLACEBO, Outcome 8 Mental state: 2c. Average total change score ‐ short term (PANSS, high=poor, data skewed).

9 Mental state: 3a. Average positive endpoint score ‐ short term (PANSS subscale, high=poor) Show forest plot

2

65

Mean Difference (IV, Random, 95% CI)

‐5.10 [‐8.86, ‐1.34]
Analysis 1.9
Comparison 1 ADJUNCTIVE LAMOTRIGINE vs ADJUNCTIVE PLACEBO, Outcome 9 Mental state: 3a. Average positive endpoint score ‐ short term (PANSS subscale, high=poor).

Comparison 1 ADJUNCTIVE LAMOTRIGINE vs ADJUNCTIVE PLACEBO, Outcome 9 Mental state: 3a. Average positive endpoint score ‐ short term (PANSS subscale, high=poor).

10 Mental state: 3b. Average positive change score ‐ short term (PANSS subscale, high change=good, data skewed) Show forest plot

Other data

No numeric data
Analysis 1.10

Study

Intervention

Least Square Mean

SD

N

Notes

Goff 2006a

Adjuvant lamotrigine

‐2.2

4.39

101

Goff 2006a

Adjuvant placebo

‐3.2

4.51

104

Goff 2006b

Adjuvant lamotrigine

‐4.4

4.18

103

Goff 2006b

Adjuvant placebo

‐3.9

4.20

104

Comparison 1 ADJUNCTIVE LAMOTRIGINE vs ADJUNCTIVE PLACEBO, Outcome 10 Mental state: 3b. Average positive change score ‐ short term (PANSS subscale, high change=good, data skewed).

11 Mental state: 4a. Average negative endpoint score ‐ short term (PANSS subscale, high=poor) Show forest plot

2

67

Mean Difference (IV, Random, 95% CI)

‐5.25 [‐7.07, ‐3.43]
Analysis 1.11
Comparison 1 ADJUNCTIVE LAMOTRIGINE vs ADJUNCTIVE PLACEBO, Outcome 11 Mental state: 4a. Average negative endpoint score ‐ short term (PANSS subscale, high=poor).

Comparison 1 ADJUNCTIVE LAMOTRIGINE vs ADJUNCTIVE PLACEBO, Outcome 11 Mental state: 4a. Average negative endpoint score ‐ short term (PANSS subscale, high=poor).

12 Mental state: 4b. Average negative endpoint score ‐ short term (SANS, high=poor) Show forest plot

1

31

Mean Difference (IV, Random, 95% CI)

‐8.80 [‐19.73, 2.13]
Analysis 1.12
Comparison 1 ADJUNCTIVE LAMOTRIGINE vs ADJUNCTIVE PLACEBO, Outcome 12 Mental state: 4b. Average negative endpoint score ‐ short term (SANS, high=poor).

Comparison 1 ADJUNCTIVE LAMOTRIGINE vs ADJUNCTIVE PLACEBO, Outcome 12 Mental state: 4b. Average negative endpoint score ‐ short term (SANS, high=poor).

13 Mental state: 4c. Average negative change score ‐ short term (SANS, high change=good, data skewed) Show forest plot

Other data

No numeric data
Analysis 1.13

Study

Intervention

Least Mean Square

SD

N

Notes

Goff 2006a

Adjuvant lamotrigine

‐2.6

12.65

97

Goff 2006a

Adjuvant placebo

‐6.2

13.16

100

Goff 2006b

Adjuvant lamotrigine

‐4.8

11.69

101

Goff 2006b

Adjuvant placebo

‐5.7

11.69

102

Comparison 1 ADJUNCTIVE LAMOTRIGINE vs ADJUNCTIVE PLACEBO, Outcome 13 Mental state: 4c. Average negative change score ‐ short term (SANS, high change=good, data skewed).

14 Mental state: 5a. Average general psychopathology endpoint score ‐ short term (PANSS, high=poor) Show forest plot

2

67

Mean Difference (IV, Random, 95% CI)

‐10.74 [‐16.53, ‐4.96]
Analysis 1.14
Comparison 1 ADJUNCTIVE LAMOTRIGINE vs ADJUNCTIVE PLACEBO, Outcome 14 Mental state: 5a. Average general psychopathology endpoint score ‐ short term (PANSS, high=poor).

Comparison 1 ADJUNCTIVE LAMOTRIGINE vs ADJUNCTIVE PLACEBO, Outcome 14 Mental state: 5a. Average general psychopathology endpoint score ‐ short term (PANSS, high=poor).

15 Mental state: 5c. Average general psychopathology change score ‐ short term (PANSS subscale, data skewed) Show forest plot

Other data

No numeric data
Analysis 1.15

Study

Intervention

Least Mean Squares

SD

N

Notes

Goff 2006a

Adjuvant lamotrigine

‐2.4

7.45

101

High change=good

Goff 2006a

Adjuvant placebo

‐3.7

7.48

104

Goff 2006b

Adjuvant lamotrigine

‐5.5

6.63

103

Goff 2006b

Adjuvant placebo

‐5.3

6.56

104

Comparison 1 ADJUNCTIVE LAMOTRIGINE vs ADJUNCTIVE PLACEBO, Outcome 15 Mental state: 5c. Average general psychopathology change score ‐ short term (PANSS subscale, data skewed).

16 Mental state: 6a. Average depression endpoint score (HAM‐D 21, high=poor) Show forest plot

1

31

Mean Difference (IV, Random, 95% CI)

0.10 [‐3.69, 3.89]
Analysis 1.16
Comparison 1 ADJUNCTIVE LAMOTRIGINE vs ADJUNCTIVE PLACEBO, Outcome 16 Mental state: 6a. Average depression endpoint score (HAM‐D 21, high=poor).

Comparison 1 ADJUNCTIVE LAMOTRIGINE vs ADJUNCTIVE PLACEBO, Outcome 16 Mental state: 6a. Average depression endpoint score (HAM‐D 21, high=poor).

17 Mental state: 6b. Average depression change score (CDSS, high change=good, data skewed) Show forest plot

Other data

No numeric data
Analysis 1.17

Study

Intervention

Least Square Mean

SD

N

Notes

Goff 2006a

Adjuvant lamotrigine

‐0.2

3.57

97

Goff 2006a

Adjuvant placebo

‐0.8

3.59

101

Goff 2006b

Adjuvant lamotrigine

‐0.8

2.96

100

Goff 2006b

Adjuvant placebo

‐1.2

2.97

102

Comparison 1 ADJUNCTIVE LAMOTRIGINE vs ADJUNCTIVE PLACEBO, Outcome 17 Mental state: 6b. Average depression change score (CDSS, high change=good, data skewed).

18 Mental state: 6c. Average depression change score ‐ short term (WHO‐5, high change=good, data skewed) Show forest plot

Other data

No numeric data
Analysis 1.18

Study

Intervention

Least Square Mean

SD

N

Notes

Goff 2006b

Adjuvant lamotrigine

2.7

22.8

86

Goff 2006b

Adjuvant placebo

1.8

22.71

86

Comparison 1 ADJUNCTIVE LAMOTRIGINE vs ADJUNCTIVE PLACEBO, Outcome 18 Mental state: 6c. Average depression change score ‐ short term (WHO‐5, high change=good, data skewed).

19 Cognitive state: 1. Treatment response (BACS) Show forest plot

2

329

Risk Ratio (M‐H, Random, 95% CI)

1.10 [0.59, 2.04]
Analysis 1.19
Comparison 1 ADJUNCTIVE LAMOTRIGINE vs ADJUNCTIVE PLACEBO, Outcome 19 Cognitive state: 1. Treatment response (BACS).

Comparison 1 ADJUNCTIVE LAMOTRIGINE vs ADJUNCTIVE PLACEBO, Outcome 19 Cognitive state: 1. Treatment response (BACS).

20 Cognitive state: 2. Average change score ‐ short term (Stroop test, high difference from baseline=good) Show forest plot

1

Mean Difference (IV, Random, 95% CI)

Subtotals only
Analysis 1.20
Comparison 1 ADJUNCTIVE LAMOTRIGINE vs ADJUNCTIVE PLACEBO, Outcome 20 Cognitive state: 2. Average change score ‐ short term (Stroop test, high difference from baseline=good).

Comparison 1 ADJUNCTIVE LAMOTRIGINE vs ADJUNCTIVE PLACEBO, Outcome 20 Cognitive state: 2. Average change score ‐ short term (Stroop test, high difference from baseline=good).

20.1 Stroop ‐ color naming time

1

36

Mean Difference (IV, Random, 95% CI)

‐29.45 [‐53.69, ‐5.21]

20.2 Stroop ‐ color naming error

1

36

Mean Difference (IV, Random, 95% CI)

‐8.28 [‐12.85, ‐3.71]

20.3 Stroop ‐ word reading time

1

36

Mean Difference (IV, Random, 95% CI)

0.61 [‐10.81, 12.03]

20.4 Stroop ‐ word reading error

1

36

Mean Difference (IV, Random, 95% CI)

‐0.33 [‐2.46, 1.80]

21 Cognitive state: 3. Average change score ‐ short term (BACS, high change=good, data skewed) Show forest plot

Other data

No numeric data
Analysis 1.21

Study

Intervention

Least Square mean

SD

N

Notes

Goff 2006a

Adjuvant lamotrigine

0.22

0.61

74

Goff 2006a

Adjuvant placebo

0.23

0.51

84

Goff 2006b

Adjuvant lamotrigine

0.44

0.68

103

Goff 2006b

Adjuvant placebo

0.19

0.70

103

Comparison 1 ADJUNCTIVE LAMOTRIGINE vs ADJUNCTIVE PLACEBO, Outcome 21 Cognitive state: 3. Average change score ‐ short term (BACS, high change=good, data skewed).

22 Leaving the study early ‐ short term Show forest plot

5

537

Risk Ratio (M‐H, Random, 95% CI)

0.96 [0.71, 1.29]
Analysis 1.22
Comparison 1 ADJUNCTIVE LAMOTRIGINE vs ADJUNCTIVE PLACEBO, Outcome 22 Leaving the study early ‐ short term.

Comparison 1 ADJUNCTIVE LAMOTRIGINE vs ADJUNCTIVE PLACEBO, Outcome 22 Leaving the study early ‐ short term.

23 Adverse effects: 1. Death, self harm, ideation about harm to self or others ‐ short term Show forest plot

2

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only
Analysis 1.23
Comparison 1 ADJUNCTIVE LAMOTRIGINE vs ADJUNCTIVE PLACEBO, Outcome 23 Adverse effects: 1. Death, self harm, ideation about harm to self or others ‐ short term.

Comparison 1 ADJUNCTIVE LAMOTRIGINE vs ADJUNCTIVE PLACEBO, Outcome 23 Adverse effects: 1. Death, self harm, ideation about harm to self or others ‐ short term.

23.1 death

2

429

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

23.2 any one or more fatalistic acts/impulses

2

429

Risk Ratio (M‐H, Random, 95% CI)

2.38 [0.90, 6.30]

23.3 suicide attempt

1

217

Risk Ratio (M‐H, Random, 95% CI)

2.97 [0.12, 72.18]

23.4 ideation ‐ homicidal

1

217

Risk Ratio (M‐H, Random, 95% CI)

4.95 [0.24, 102.01]

23.5 ideation ‐ suicidal

2

429

Risk Ratio (M‐H, Random, 95% CI)

1.05 [0.15, 7.06]

24 Adverse effects: 2a. Specific ‐ any adverse effect ‐ short term Show forest plot

2

429

Risk Ratio (M‐H, Random, 95% CI)

1.19 [1.02, 1.38]
Analysis 1.24
Comparison 1 ADJUNCTIVE LAMOTRIGINE vs ADJUNCTIVE PLACEBO, Outcome 24 Adverse effects: 2a. Specific ‐ any adverse effect ‐ short term.

Comparison 1 ADJUNCTIVE LAMOTRIGINE vs ADJUNCTIVE PLACEBO, Outcome 24 Adverse effects: 2a. Specific ‐ any adverse effect ‐ short term.

25 Adverse effects: 2b. Specific ‐ cardiovascular ‐ short term Show forest plot

2

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only
Analysis 1.25
Comparison 1 ADJUNCTIVE LAMOTRIGINE vs ADJUNCTIVE PLACEBO, Outcome 25 Adverse effects: 2b. Specific ‐ cardiovascular ‐ short term.

Comparison 1 ADJUNCTIVE LAMOTRIGINE vs ADJUNCTIVE PLACEBO, Outcome 25 Adverse effects: 2b. Specific ‐ cardiovascular ‐ short term.

25.1 chest pain

2

429

Risk Ratio (M‐H, Random, 95% CI)

1.68 [0.18, 15.99]

25.2 electrocardiogram abnormal

1

212

Risk Ratio (M‐H, Random, 95% CI)

3.00 [0.12, 72.82]

25.3 hypertension

1

212

Risk Ratio (M‐H, Random, 95% CI)

2.50 [0.50, 12.60]

25.4 tachycardia

1

212

Risk Ratio (M‐H, Random, 95% CI)

0.33 [0.01, 8.09]

26 Adverse effects: 2c. Specific ‐ dermatological ‐ short term Show forest plot

3

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only
Analysis 1.26
Comparison 1 ADJUNCTIVE LAMOTRIGINE vs ADJUNCTIVE PLACEBO, Outcome 26 Adverse effects: 2c. Specific ‐ dermatological ‐ short term.

Comparison 1 ADJUNCTIVE LAMOTRIGINE vs ADJUNCTIVE PLACEBO, Outcome 26 Adverse effects: 2c. Specific ‐ dermatological ‐ short term.

26.27 hair loss

1

36

Risk Ratio (M‐H, Random, 95% CI)

3.00 [0.13, 69.09]

26.34 itching

1

36

Risk Ratio (M‐H, Random, 95% CI)

4.0 [0.49, 32.39]

26.45 rash

3

465

Risk Ratio (M‐H, Random, 95% CI)

0.74 [0.24, 2.28]

27 Adverse effects: 2d. Specific ‐ gastrointestinal ‐ short term Show forest plot

3

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only
Analysis 1.27
Comparison 1 ADJUNCTIVE LAMOTRIGINE vs ADJUNCTIVE PLACEBO, Outcome 27 Adverse effects: 2d. Specific ‐ gastrointestinal ‐ short term.

Comparison 1 ADJUNCTIVE LAMOTRIGINE vs ADJUNCTIVE PLACEBO, Outcome 27 Adverse effects: 2d. Specific ‐ gastrointestinal ‐ short term.

27.1 constipation

1

212

Risk Ratio (M‐H, Random, 95% CI)

0.33 [0.04, 3.15]

27.2 decreased appetite

1

217

Risk Ratio (M‐H, Random, 95% CI)

0.11 [0.01, 2.02]

27.3 diarrhea

3

465

Risk Ratio (M‐H, Random, 95% CI)

1.56 [0.39, 6.16]

27.4 dyspepsia

1

212

Risk Ratio (M‐H, Random, 95% CI)

4.0 [0.45, 35.20]

27.5 nausea

3

465

Risk Ratio (M‐H, Random, 95% CI)

2.26 [1.05, 4.88]

27.6 vomiting

2

253

Risk Ratio (M‐H, Random, 95% CI)

3.17 [0.77, 13.02]

28 Adverse effects: 2e. Specific ‐ metabolic parameters ‐ short term Show forest plot

2

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only
Analysis 1.28
Comparison 1 ADJUNCTIVE LAMOTRIGINE vs ADJUNCTIVE PLACEBO, Outcome 28 Adverse effects: 2e. Specific ‐ metabolic parameters ‐ short term.

Comparison 1 ADJUNCTIVE LAMOTRIGINE vs ADJUNCTIVE PLACEBO, Outcome 28 Adverse effects: 2e. Specific ‐ metabolic parameters ‐ short term.

28.1 alanine aminotransferase increase

1

217

Risk Ratio (M‐H, Random, 95% CI)

2.97 [0.12, 72.18]

28.2 aspartate aminotransferase

1

217

Risk Ratio (M‐H, Random, 95% CI)

2.97 [0.12, 72.18]

28.3 blood creatine phosphokinase

1

212

Risk Ratio (M‐H, Random, 95% CI)

0.33 [0.01, 8.09]

28.4 blood glucose increase

1

212

Risk Ratio (M‐H, Random, 95% CI)

1.5 [0.26, 8.80]

29 Adverse effects: 2f. Specific ‐ neurological ‐ short term Show forest plot

3

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only
Analysis 1.29
Comparison 1 ADJUNCTIVE LAMOTRIGINE vs ADJUNCTIVE PLACEBO, Outcome 29 Adverse effects: 2f. Specific ‐ neurological ‐ short term.

Comparison 1 ADJUNCTIVE LAMOTRIGINE vs ADJUNCTIVE PLACEBO, Outcome 29 Adverse effects: 2f. Specific ‐ neurological ‐ short term.

29.1 ataxia

1

36

Risk Ratio (M‐H, Random, 95% CI)

5.00 [0.26, 97.37]

29.2 blurred vision

1

36

Risk Ratio (M‐H, Random, 95% CI)

2.0 [0.20, 20.15]

29.3 dizziness

3

465

Risk Ratio (M‐H, Random, 95% CI)

1.17 [0.51, 2.70]

29.4 headache

3

465

Risk Ratio (M‐H, Random, 95% CI)

1.36 [0.88, 2.08]

29.5 loss of consciousness

1

212

Risk Ratio (M‐H, Random, 95% CI)

5.0 [0.24, 102.92]

29.6 paraesthesia

1

212

Risk Ratio (M‐H, Random, 95% CI)

3.00 [0.12, 72.82]

29.7 hypoaesthesia

1

212

Risk Ratio (M‐H, Random, 95% CI)

7.00 [0.37, 133.88]

29.8 tremor

1

217

Risk Ratio (M‐H, Random, 95% CI)

4.95 [0.59, 41.71]

30 Adverse effects: 2g. Specific ‐ psychiatric ‐ short term Show forest plot

2

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only
Analysis 1.30
Comparison 1 ADJUNCTIVE LAMOTRIGINE vs ADJUNCTIVE PLACEBO, Outcome 30 Adverse effects: 2g. Specific ‐ psychiatric ‐ short term.

Comparison 1 ADJUNCTIVE LAMOTRIGINE vs ADJUNCTIVE PLACEBO, Outcome 30 Adverse effects: 2g. Specific ‐ psychiatric ‐ short term.

30.1 aggression

1

217

Risk Ratio (M‐H, Random, 95% CI)

2.97 [0.12, 72.18]

30.2 agitation

1

212

Risk Ratio (M‐H, Random, 95% CI)

0.5 [0.09, 2.67]

30.3 anxiety

2

429

Risk Ratio (M‐H, Random, 95% CI)

0.73 [0.09, 5.76]

30.4 crying

1

212

Risk Ratio (M‐H, Random, 95% CI)

0.33 [0.01, 8.09]

30.5 hallucination, auditory

1

217

Risk Ratio (M‐H, Random, 95% CI)

10.90 [0.61, 194.74]

30.6 insomnia

2

429

Risk Ratio (M‐H, Random, 95% CI)

2.02 [0.04, 96.25]

30.7 paranoia

2

429

Risk Ratio (M‐H, Random, 95% CI)

1.99 [0.37, 10.75]

30.8 somnolence

2

429

Risk Ratio (M‐H, Random, 95% CI)

1.21 [0.51, 2.87]

31 Adverse effects: 2h. Specific ‐ respiratory ‐ short term Show forest plot

1

424

Risk Ratio (M‐H, Fixed, 95% CI)

3.0 [0.48, 18.89]
Analysis 1.31
Comparison 1 ADJUNCTIVE LAMOTRIGINE vs ADJUNCTIVE PLACEBO, Outcome 31 Adverse effects: 2h. Specific ‐ respiratory ‐ short term.

Comparison 1 ADJUNCTIVE LAMOTRIGINE vs ADJUNCTIVE PLACEBO, Outcome 31 Adverse effects: 2h. Specific ‐ respiratory ‐ short term.

31.1 cough

1

212

Risk Ratio (M‐H, Fixed, 95% CI)

7.0 [0.37, 133.88]

31.2 influenza

1

212

Risk Ratio (M‐H, Fixed, 95% CI)

1.0 [0.06, 15.78]

32 Adverse effects: 2i. Specific ‐ others ‐ short term Show forest plot

2

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only
Analysis 1.32
Comparison 1 ADJUNCTIVE LAMOTRIGINE vs ADJUNCTIVE PLACEBO, Outcome 32 Adverse effects: 2i. Specific ‐ others ‐ short term.

Comparison 1 ADJUNCTIVE LAMOTRIGINE vs ADJUNCTIVE PLACEBO, Outcome 32 Adverse effects: 2i. Specific ‐ others ‐ short term.

32.1 abnormal dreams

1

217

Risk Ratio (M‐H, Random, 95% CI)

0.33 [0.01, 8.02]

32.2 asthenia

1

217

Risk Ratio (M‐H, Random, 95% CI)

0.33 [0.01, 8.02]

32.3 back pain

1

217

Risk Ratio (M‐H, Random, 95% CI)

0.99 [0.30, 3.33]

32.4 dry mouth

1

212

Risk Ratio (M‐H, Random, 95% CI)

1.0 [0.21, 4.84]

32.5 fatigue

1

217

Risk Ratio (M‐H, Random, 95% CI)

1.39 [0.45, 4.24]

32.6 lymphadenopathy

2

429

Risk Ratio (M‐H, Random, 95% CI)

2.99 [0.31, 28.48]

32.7 urine abnormality

1

212

Risk Ratio (M‐H, Random, 95% CI)

3.00 [0.12, 72.82]

32.8 weight increase

1

212

Risk Ratio (M‐H, Random, 95% CI)

3.00 [0.12, 72.82]

33 Adverse effects: 3. Events ‐ co‐incident with trial ‐ short term Show forest plot

2

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only
Analysis 1.33
Comparison 1 ADJUNCTIVE LAMOTRIGINE vs ADJUNCTIVE PLACEBO, Outcome 33 Adverse effects: 3. Events ‐ co‐incident with trial ‐ short term.

Comparison 1 ADJUNCTIVE LAMOTRIGINE vs ADJUNCTIVE PLACEBO, Outcome 33 Adverse effects: 3. Events ‐ co‐incident with trial ‐ short term.

33.1 abscess

1

212

Risk Ratio (M‐H, Random, 95% CI)

3.00 [0.12, 72.82]

33.2 arthropod bite

1

212

Risk Ratio (M‐H, Random, 95% CI)

0.33 [0.01, 8.09]

33.3 endometrial cancer

1

212

Risk Ratio (M‐H, Random, 95% CI)

3.00 [0.12, 72.82]

33.5 joint injury

1

217

Risk Ratio (M‐H, Random, 95% CI)

2.97 [0.12, 72.18]

33.6 local swelling

1

217

Risk Ratio (M‐H, Random, 95% CI)

2.97 [0.12, 72.18]

33.7 nasopharyngitis

2

429

Risk Ratio (M‐H, Random, 95% CI)

1.42 [0.28, 7.15]

33.8 pharyngolaryngeal pain

1

212

Risk Ratio (M‐H, Random, 95% CI)

3.00 [0.12, 72.82]

33.9 post‐procedural pain

1

217

Risk Ratio (M‐H, Random, 95% CI)

2.97 [0.12, 72.18]

33.10 tooth abscess

1

217

Risk Ratio (M‐H, Random, 95% CI)

2.97 [0.12, 72.18]

33.11 toothache

1

217

Risk Ratio (M‐H, Random, 95% CI)

0.40 [0.08, 2.00]

33.12 upper respiratory tract infection

2

429

Risk Ratio (M‐H, Random, 95% CI)

1.05 [0.22, 4.94]

34 Adverse effects: 4a. Movement disorders ‐ average endpoint score (ESRS, high = poor, data skewed) Show forest plot

Other data

No numeric data
Analysis 1.34

Study

Intervention

Mean

SD

N

Notes

Akhondzadeh 2005

Lamotrigine

2.93

2.99

18

p=0.78

Akhondzadeh 2005

Placebo

3.25

3.27

18

Comparison 1 ADJUNCTIVE LAMOTRIGINE vs ADJUNCTIVE PLACEBO, Outcome 34 Adverse effects: 4a. Movement disorders ‐ average endpoint score (ESRS, high = poor, data skewed).

35 Adverse effects: 4b. Movement disorders ‐ average dose (biperiden, mg, high = poor, data skewed) Show forest plot

Other data

No numeric data
Analysis 1.35

Study

Intervention

Mean

SD

N

Notes

Akhondzadeh 2005

Lamotrigine

100.33

81.38

17

p=0.19

Akhondzadeh 2005

Placebo

137.66

87.00

17

Comparison 1 ADJUNCTIVE LAMOTRIGINE vs ADJUNCTIVE PLACEBO, Outcome 35 Adverse effects: 4b. Movement disorders ‐ average dose (biperiden, mg, high = poor, data skewed).

Post‐hoc subgroup analysis: Heterogenous data for average change scores (PANSS total scores, high = poor)
Figuras y tablas -
Figure 1

Post‐hoc subgroup analysis: Heterogenous data for average change scores (PANSS total scores, high = poor)

Ir a la figura de la revisiónAbrir en una pestaña nueva

Comparison 1 ADJUNCTIVE LAMOTRIGINE vs ADJUNCTIVE PLACEBO, Outcome 1 Global state: 1.Global improvement (CGI‐I).
Figuras y tablas -
Analysis 1.1

Comparison 1 ADJUNCTIVE LAMOTRIGINE vs ADJUNCTIVE PLACEBO, Outcome 1 Global state: 1.Global improvement (CGI‐I).

Ir a la figura de la revisiónAbrir en una pestaña nueva

Study

Intervention

Least Mean Square

SD

N

Notes

Goff 2006a

Adjuvant lamotrigine

‐0.2

0.82

101

Goff 2006a

Adjuvant placebo

‐0.5

0.82

104

Goff 2006b

Adjuvant lamotrigine

‐0.5

0.72

104

Goff 2006b

Adjuvant placebo

‐0.4

0.72

104

Figuras y tablas -
Analysis 1.2

Comparison 1 ADJUNCTIVE LAMOTRIGINE vs ADJUNCTIVE PLACEBO, Outcome 2 Global state: 2. Average total change score ‐ short term (CGI‐S, high change=good, data skewed).

Ir a la figura de la revisión

Study

Intervention

Least Square Mean

SD

N

Notes

Goff 2006b

Adjuvant lamotrigine

0.07

7.18

87

Goff 2006b

Adjuvant placebo

‐0.31

7.22

88

Figuras y tablas -
Analysis 1.3

Comparison 1 ADJUNCTIVE LAMOTRIGINE vs ADJUNCTIVE PLACEBO, Outcome 3 Global state: 3. Average physical health change score ‐ short term (SF‐36, high change=good, data skewed).

Ir a la figura de la revisión

Study

Intervention

Least Square Mean

SD

N

Notes

Goff 2006b

Adjuvant lamotrigine

0.21

8.21

87

Goff 2006b

Adjuvant placebo

1.32

8.16

88

Figuras y tablas -
Analysis 1.4

Comparison 1 ADJUNCTIVE LAMOTRIGINE vs ADJUNCTIVE PLACEBO, Outcome 4 Global state: 4. Average mental health change score ‐ short term (SF‐36, high change=good, data skewed).

Ir a la figura de la revisión

Comparison 1 ADJUNCTIVE LAMOTRIGINE vs ADJUNCTIVE PLACEBO, Outcome 5 Mental state: 1.Treatment responders (> 20% reduction in PANSS total).
Figuras y tablas -
Analysis 1.5

Comparison 1 ADJUNCTIVE LAMOTRIGINE vs ADJUNCTIVE PLACEBO, Outcome 5 Mental state: 1.Treatment responders (> 20% reduction in PANSS total).

Ir a la figura de la revisiónAbrir en una pestaña nueva

Comparison 1 ADJUNCTIVE LAMOTRIGINE vs ADJUNCTIVE PLACEBO, Outcome 6 Mental state: 2a. Average total endpoint score ‐ short term (PANSS, high=poor).
Figuras y tablas -
Analysis 1.6

Comparison 1 ADJUNCTIVE LAMOTRIGINE vs ADJUNCTIVE PLACEBO, Outcome 6 Mental state: 2a. Average total endpoint score ‐ short term (PANSS, high=poor).

Ir a la figura de la revisiónAbrir en una pestaña nueva

Comparison 1 ADJUNCTIVE LAMOTRIGINE vs ADJUNCTIVE PLACEBO, Outcome 7 Mental state: 2b. Average total endpoint score ‐ short term (BPRS, high=poor).
Figuras y tablas -
Analysis 1.7

Comparison 1 ADJUNCTIVE LAMOTRIGINE vs ADJUNCTIVE PLACEBO, Outcome 7 Mental state: 2b. Average total endpoint score ‐ short term (BPRS, high=poor).

Ir a la figura de la revisiónAbrir en una pestaña nueva

Study

Intervention

Least Square Mean

SD

N

Notes

Goff 2006a

Adjuvant lamotrigine

‐6.0

13.77

101

Goff 2006a

Adjuvant placebo

‐8.2

13.84

104

Goff 2006b

Adjuvant lamotrigine

‐12.9

12.34

103

Goff 2006b

Adjuvant placebo

‐12.0

12.40

104

Figuras y tablas -
Analysis 1.8

Comparison 1 ADJUNCTIVE LAMOTRIGINE vs ADJUNCTIVE PLACEBO, Outcome 8 Mental state: 2c. Average total change score ‐ short term (PANSS, high=poor, data skewed).

Ir a la figura de la revisión

Comparison 1 ADJUNCTIVE LAMOTRIGINE vs ADJUNCTIVE PLACEBO, Outcome 9 Mental state: 3a. Average positive endpoint score ‐ short term (PANSS subscale, high=poor).
Figuras y tablas -
Analysis 1.9

Comparison 1 ADJUNCTIVE LAMOTRIGINE vs ADJUNCTIVE PLACEBO, Outcome 9 Mental state: 3a. Average positive endpoint score ‐ short term (PANSS subscale, high=poor).

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Study

Intervention

Least Square Mean

SD

N

Notes

Goff 2006a

Adjuvant lamotrigine

‐2.2

4.39

101

Goff 2006a

Adjuvant placebo

‐3.2

4.51

104

Goff 2006b

Adjuvant lamotrigine

‐4.4

4.18

103

Goff 2006b

Adjuvant placebo

‐3.9

4.20

104

Figuras y tablas -
Analysis 1.10

Comparison 1 ADJUNCTIVE LAMOTRIGINE vs ADJUNCTIVE PLACEBO, Outcome 10 Mental state: 3b. Average positive change score ‐ short term (PANSS subscale, high change=good, data skewed).

Ir a la figura de la revisión

Comparison 1 ADJUNCTIVE LAMOTRIGINE vs ADJUNCTIVE PLACEBO, Outcome 11 Mental state: 4a. Average negative endpoint score ‐ short term (PANSS subscale, high=poor).
Figuras y tablas -
Analysis 1.11

Comparison 1 ADJUNCTIVE LAMOTRIGINE vs ADJUNCTIVE PLACEBO, Outcome 11 Mental state: 4a. Average negative endpoint score ‐ short term (PANSS subscale, high=poor).

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Comparison 1 ADJUNCTIVE LAMOTRIGINE vs ADJUNCTIVE PLACEBO, Outcome 12 Mental state: 4b. Average negative endpoint score ‐ short term (SANS, high=poor).
Figuras y tablas -
Analysis 1.12

Comparison 1 ADJUNCTIVE LAMOTRIGINE vs ADJUNCTIVE PLACEBO, Outcome 12 Mental state: 4b. Average negative endpoint score ‐ short term (SANS, high=poor).

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Study

Intervention

Least Mean Square

SD

N

Notes

Goff 2006a

Adjuvant lamotrigine

‐2.6

12.65

97

Goff 2006a

Adjuvant placebo

‐6.2

13.16

100

Goff 2006b

Adjuvant lamotrigine

‐4.8

11.69

101

Goff 2006b

Adjuvant placebo

‐5.7

11.69

102

Figuras y tablas -
Analysis 1.13

Comparison 1 ADJUNCTIVE LAMOTRIGINE vs ADJUNCTIVE PLACEBO, Outcome 13 Mental state: 4c. Average negative change score ‐ short term (SANS, high change=good, data skewed).

Ir a la figura de la revisión

Comparison 1 ADJUNCTIVE LAMOTRIGINE vs ADJUNCTIVE PLACEBO, Outcome 14 Mental state: 5a. Average general psychopathology endpoint score ‐ short term (PANSS, high=poor).
Figuras y tablas -
Analysis 1.14

Comparison 1 ADJUNCTIVE LAMOTRIGINE vs ADJUNCTIVE PLACEBO, Outcome 14 Mental state: 5a. Average general psychopathology endpoint score ‐ short term (PANSS, high=poor).

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Study

Intervention

Least Mean Squares

SD

N

Notes

Goff 2006a

Adjuvant lamotrigine

‐2.4

7.45

101

High change=good

Goff 2006a

Adjuvant placebo

‐3.7

7.48

104

Goff 2006b

Adjuvant lamotrigine

‐5.5

6.63

103

Goff 2006b

Adjuvant placebo

‐5.3

6.56

104

Figuras y tablas -
Analysis 1.15

Comparison 1 ADJUNCTIVE LAMOTRIGINE vs ADJUNCTIVE PLACEBO, Outcome 15 Mental state: 5c. Average general psychopathology change score ‐ short term (PANSS subscale, data skewed).

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Comparison 1 ADJUNCTIVE LAMOTRIGINE vs ADJUNCTIVE PLACEBO, Outcome 16 Mental state: 6a. Average depression endpoint score (HAM‐D 21, high=poor).
Figuras y tablas -
Analysis 1.16

Comparison 1 ADJUNCTIVE LAMOTRIGINE vs ADJUNCTIVE PLACEBO, Outcome 16 Mental state: 6a. Average depression endpoint score (HAM‐D 21, high=poor).

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Study

Intervention

Least Square Mean

SD

N

Notes

Goff 2006a

Adjuvant lamotrigine

‐0.2

3.57

97

Goff 2006a

Adjuvant placebo

‐0.8

3.59

101

Goff 2006b

Adjuvant lamotrigine

‐0.8

2.96

100

Goff 2006b

Adjuvant placebo

‐1.2

2.97

102

Figuras y tablas -
Analysis 1.17

Comparison 1 ADJUNCTIVE LAMOTRIGINE vs ADJUNCTIVE PLACEBO, Outcome 17 Mental state: 6b. Average depression change score (CDSS, high change=good, data skewed).

Ir a la figura de la revisión

Study

Intervention

Least Square Mean

SD

N

Notes

Goff 2006b

Adjuvant lamotrigine

2.7

22.8

86

Goff 2006b

Adjuvant placebo

1.8

22.71

86

Figuras y tablas -
Analysis 1.18

Comparison 1 ADJUNCTIVE LAMOTRIGINE vs ADJUNCTIVE PLACEBO, Outcome 18 Mental state: 6c. Average depression change score ‐ short term (WHO‐5, high change=good, data skewed).

Ir a la figura de la revisión

Comparison 1 ADJUNCTIVE LAMOTRIGINE vs ADJUNCTIVE PLACEBO, Outcome 19 Cognitive state: 1. Treatment response (BACS).
Figuras y tablas -
Analysis 1.19

Comparison 1 ADJUNCTIVE LAMOTRIGINE vs ADJUNCTIVE PLACEBO, Outcome 19 Cognitive state: 1. Treatment response (BACS).

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Comparison 1 ADJUNCTIVE LAMOTRIGINE vs ADJUNCTIVE PLACEBO, Outcome 20 Cognitive state: 2. Average change score ‐ short term (Stroop test, high difference from baseline=good).
Figuras y tablas -
Analysis 1.20

Comparison 1 ADJUNCTIVE LAMOTRIGINE vs ADJUNCTIVE PLACEBO, Outcome 20 Cognitive state: 2. Average change score ‐ short term (Stroop test, high difference from baseline=good).

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Study

Intervention

Least Square mean

SD

N

Notes

Goff 2006a

Adjuvant lamotrigine

0.22

0.61

74

Goff 2006a

Adjuvant placebo

0.23

0.51

84

Goff 2006b

Adjuvant lamotrigine

0.44

0.68

103

Goff 2006b

Adjuvant placebo

0.19

0.70

103

Figuras y tablas -
Analysis 1.21

Comparison 1 ADJUNCTIVE LAMOTRIGINE vs ADJUNCTIVE PLACEBO, Outcome 21 Cognitive state: 3. Average change score ‐ short term (BACS, high change=good, data skewed).

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Comparison 1 ADJUNCTIVE LAMOTRIGINE vs ADJUNCTIVE PLACEBO, Outcome 22 Leaving the study early ‐ short term.
Figuras y tablas -
Analysis 1.22

Comparison 1 ADJUNCTIVE LAMOTRIGINE vs ADJUNCTIVE PLACEBO, Outcome 22 Leaving the study early ‐ short term.

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Comparison 1 ADJUNCTIVE LAMOTRIGINE vs ADJUNCTIVE PLACEBO, Outcome 23 Adverse effects: 1. Death, self harm, ideation about harm to self or others ‐ short term.
Figuras y tablas -
Analysis 1.23

Comparison 1 ADJUNCTIVE LAMOTRIGINE vs ADJUNCTIVE PLACEBO, Outcome 23 Adverse effects: 1. Death, self harm, ideation about harm to self or others ‐ short term.

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Comparison 1 ADJUNCTIVE LAMOTRIGINE vs ADJUNCTIVE PLACEBO, Outcome 24 Adverse effects: 2a. Specific ‐ any adverse effect ‐ short term.
Figuras y tablas -
Analysis 1.24

Comparison 1 ADJUNCTIVE LAMOTRIGINE vs ADJUNCTIVE PLACEBO, Outcome 24 Adverse effects: 2a. Specific ‐ any adverse effect ‐ short term.

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Comparison 1 ADJUNCTIVE LAMOTRIGINE vs ADJUNCTIVE PLACEBO, Outcome 25 Adverse effects: 2b. Specific ‐ cardiovascular ‐ short term.
Figuras y tablas -
Analysis 1.25

Comparison 1 ADJUNCTIVE LAMOTRIGINE vs ADJUNCTIVE PLACEBO, Outcome 25 Adverse effects: 2b. Specific ‐ cardiovascular ‐ short term.

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Comparison 1 ADJUNCTIVE LAMOTRIGINE vs ADJUNCTIVE PLACEBO, Outcome 26 Adverse effects: 2c. Specific ‐ dermatological ‐ short term.
Figuras y tablas -
Analysis 1.26

Comparison 1 ADJUNCTIVE LAMOTRIGINE vs ADJUNCTIVE PLACEBO, Outcome 26 Adverse effects: 2c. Specific ‐ dermatological ‐ short term.

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Comparison 1 ADJUNCTIVE LAMOTRIGINE vs ADJUNCTIVE PLACEBO, Outcome 27 Adverse effects: 2d. Specific ‐ gastrointestinal ‐ short term.
Figuras y tablas -
Analysis 1.27

Comparison 1 ADJUNCTIVE LAMOTRIGINE vs ADJUNCTIVE PLACEBO, Outcome 27 Adverse effects: 2d. Specific ‐ gastrointestinal ‐ short term.

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Comparison 1 ADJUNCTIVE LAMOTRIGINE vs ADJUNCTIVE PLACEBO, Outcome 28 Adverse effects: 2e. Specific ‐ metabolic parameters ‐ short term.
Figuras y tablas -
Analysis 1.28

Comparison 1 ADJUNCTIVE LAMOTRIGINE vs ADJUNCTIVE PLACEBO, Outcome 28 Adverse effects: 2e. Specific ‐ metabolic parameters ‐ short term.

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Comparison 1 ADJUNCTIVE LAMOTRIGINE vs ADJUNCTIVE PLACEBO, Outcome 29 Adverse effects: 2f. Specific ‐ neurological ‐ short term.
Figuras y tablas -
Analysis 1.29

Comparison 1 ADJUNCTIVE LAMOTRIGINE vs ADJUNCTIVE PLACEBO, Outcome 29 Adverse effects: 2f. Specific ‐ neurological ‐ short term.

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Comparison 1 ADJUNCTIVE LAMOTRIGINE vs ADJUNCTIVE PLACEBO, Outcome 30 Adverse effects: 2g. Specific ‐ psychiatric ‐ short term.
Figuras y tablas -
Analysis 1.30

Comparison 1 ADJUNCTIVE LAMOTRIGINE vs ADJUNCTIVE PLACEBO, Outcome 30 Adverse effects: 2g. Specific ‐ psychiatric ‐ short term.

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Comparison 1 ADJUNCTIVE LAMOTRIGINE vs ADJUNCTIVE PLACEBO, Outcome 31 Adverse effects: 2h. Specific ‐ respiratory ‐ short term.
Figuras y tablas -
Analysis 1.31

Comparison 1 ADJUNCTIVE LAMOTRIGINE vs ADJUNCTIVE PLACEBO, Outcome 31 Adverse effects: 2h. Specific ‐ respiratory ‐ short term.

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Comparison 1 ADJUNCTIVE LAMOTRIGINE vs ADJUNCTIVE PLACEBO, Outcome 32 Adverse effects: 2i. Specific ‐ others ‐ short term.
Figuras y tablas -
Analysis 1.32

Comparison 1 ADJUNCTIVE LAMOTRIGINE vs ADJUNCTIVE PLACEBO, Outcome 32 Adverse effects: 2i. Specific ‐ others ‐ short term.

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Comparison 1 ADJUNCTIVE LAMOTRIGINE vs ADJUNCTIVE PLACEBO, Outcome 33 Adverse effects: 3. Events ‐ co‐incident with trial ‐ short term.
Figuras y tablas -
Analysis 1.33

Comparison 1 ADJUNCTIVE LAMOTRIGINE vs ADJUNCTIVE PLACEBO, Outcome 33 Adverse effects: 3. Events ‐ co‐incident with trial ‐ short term.

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Study

Intervention

Mean

SD

N

Notes

Akhondzadeh 2005

Lamotrigine

2.93

2.99

18

p=0.78

Akhondzadeh 2005

Placebo

3.25

3.27

18

Figuras y tablas -
Analysis 1.34

Comparison 1 ADJUNCTIVE LAMOTRIGINE vs ADJUNCTIVE PLACEBO, Outcome 34 Adverse effects: 4a. Movement disorders ‐ average endpoint score (ESRS, high = poor, data skewed).

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Study

Intervention

Mean

SD

N

Notes

Akhondzadeh 2005

Lamotrigine

100.33

81.38

17

p=0.19

Akhondzadeh 2005

Placebo

137.66

87.00

17

Figuras y tablas -
Analysis 1.35

Comparison 1 ADJUNCTIVE LAMOTRIGINE vs ADJUNCTIVE PLACEBO, Outcome 35 Adverse effects: 4b. Movement disorders ‐ average dose (biperiden, mg, high = poor, data skewed).

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Table 1. Suggestions for a trial of lamotrigine for schizophrenia

Methods

Participants

Interventions

Outcomes

Notes

Allocation: centralised sequence generation with table of random numbers or computer generated code, stratified by severity of illness, sequence concealed till interventions assigned.
Blinding: those recruiting and assigning participants, those administering intervention, those assessing outcomes, all blind to allocated group, masking by means of identical looking tablets in same schedules.
Duration: minimum of 24 weeks.

Diagnosis: schizophrenia (DSM IV), subtypes and schizoaffective disorder included and numbers in each category clearly reported.
N=300.*
Age: adults.
Sex: men and women.
Setting: anywhere.
History: baseline score on scale such as BPRS or PANSS, stratified by cutoff points into moderate and severe illness, taking routine drugs except lamotrigine or other anticonvulsants.
Exclusion: allergy to lamotrigine, pregnant or lactating women, participation in other drug trials.

1. Lamotrigine: dose 400 mg/ day + routine antipsychotic therapy. N=150.
2. Placebo + routine antipsychotic therapy. N=150.

Qualtiy of life: healthy days,** SF‐36.
Service outcomes: days in hospital, time attending psychiatric outpatient clinic.
Satisfaction with care: patients/carers.
Global state: CGI.***
Mental state: CGI.
Functioning.
Adverse effects: including mortality.
Cognitive function.

* size of study to detect a 10% difference in improvement with 80% certainity.

** Primary outcome.

*** If scales are used to measure outcome then there should be binary cut off points, defined before study starts, of clinically important improvement.

Figuras y tablas -
Table 1. Suggestions for a trial of lamotrigine for schizophrenia
Ir a la tabla de la revisión
Comparison 1. ADJUNCTIVE LAMOTRIGINE vs ADJUNCTIVE PLACEBO

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Global state: 1.Global improvement (CGI‐I) Show forest plot

1

208

Risk Ratio (M‐H, Random, 95% CI)

1.06 [0.73, 1.54]

2 Global state: 2. Average total change score ‐ short term (CGI‐S, high change=good, data skewed) Show forest plot

Other data

No numeric data

3 Global state: 3. Average physical health change score ‐ short term (SF‐36, high change=good, data skewed) Show forest plot

Other data

No numeric data

4 Global state: 4. Average mental health change score ‐ short term (SF‐36, high change=good, data skewed) Show forest plot

Other data

No numeric data

5 Mental state: 1.Treatment responders (> 20% reduction in PANSS total) Show forest plot

3

297

Risk Ratio (M‐H, Random, 95% CI)

1.26 [0.81, 1.97]

6 Mental state: 2a. Average total endpoint score ‐ short term (PANSS, high=poor) Show forest plot

2

67

Mean Difference (IV, Random, 95% CI)

‐16.88 [‐25.18, ‐8.57]

7 Mental state: 2b. Average total endpoint score ‐ short term (BPRS, high=poor) Show forest plot

1

31

Mean Difference (IV, Random, 95% CI)

‐2.80 [‐12.44, 6.84]

8 Mental state: 2c. Average total change score ‐ short term (PANSS, high=poor, data skewed) Show forest plot

Other data

No numeric data

9 Mental state: 3a. Average positive endpoint score ‐ short term (PANSS subscale, high=poor) Show forest plot

2

65

Mean Difference (IV, Random, 95% CI)

‐5.10 [‐8.86, ‐1.34]

10 Mental state: 3b. Average positive change score ‐ short term (PANSS subscale, high change=good, data skewed) Show forest plot

Other data

No numeric data

11 Mental state: 4a. Average negative endpoint score ‐ short term (PANSS subscale, high=poor) Show forest plot

2

67

Mean Difference (IV, Random, 95% CI)

‐5.25 [‐7.07, ‐3.43]

12 Mental state: 4b. Average negative endpoint score ‐ short term (SANS, high=poor) Show forest plot

1

31

Mean Difference (IV, Random, 95% CI)

‐8.80 [‐19.73, 2.13]

13 Mental state: 4c. Average negative change score ‐ short term (SANS, high change=good, data skewed) Show forest plot

Other data

No numeric data

14 Mental state: 5a. Average general psychopathology endpoint score ‐ short term (PANSS, high=poor) Show forest plot

2

67

Mean Difference (IV, Random, 95% CI)

‐10.74 [‐16.53, ‐4.96]

15 Mental state: 5c. Average general psychopathology change score ‐ short term (PANSS subscale, data skewed) Show forest plot

Other data

No numeric data

16 Mental state: 6a. Average depression endpoint score (HAM‐D 21, high=poor) Show forest plot

1

31

Mean Difference (IV, Random, 95% CI)

0.10 [‐3.69, 3.89]

17 Mental state: 6b. Average depression change score (CDSS, high change=good, data skewed) Show forest plot

Other data

No numeric data

18 Mental state: 6c. Average depression change score ‐ short term (WHO‐5, high change=good, data skewed) Show forest plot

Other data

No numeric data

19 Cognitive state: 1. Treatment response (BACS) Show forest plot

2

329

Risk Ratio (M‐H, Random, 95% CI)

1.10 [0.59, 2.04]

20 Cognitive state: 2. Average change score ‐ short term (Stroop test, high difference from baseline=good) Show forest plot

1

Mean Difference (IV, Random, 95% CI)

Subtotals only

20.1 Stroop ‐ color naming time

1

36

Mean Difference (IV, Random, 95% CI)

‐29.45 [‐53.69, ‐5.21]

20.2 Stroop ‐ color naming error

1

36

Mean Difference (IV, Random, 95% CI)

‐8.28 [‐12.85, ‐3.71]

20.3 Stroop ‐ word reading time

1

36

Mean Difference (IV, Random, 95% CI)

0.61 [‐10.81, 12.03]

20.4 Stroop ‐ word reading error

1

36

Mean Difference (IV, Random, 95% CI)

‐0.33 [‐2.46, 1.80]

21 Cognitive state: 3. Average change score ‐ short term (BACS, high change=good, data skewed) Show forest plot

Other data

No numeric data

22 Leaving the study early ‐ short term Show forest plot

5

537

Risk Ratio (M‐H, Random, 95% CI)

0.96 [0.71, 1.29]

23 Adverse effects: 1. Death, self harm, ideation about harm to self or others ‐ short term Show forest plot

2

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

23.1 death

2

429

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

23.2 any one or more fatalistic acts/impulses

2

429

Risk Ratio (M‐H, Random, 95% CI)

2.38 [0.90, 6.30]

23.3 suicide attempt

1

217

Risk Ratio (M‐H, Random, 95% CI)

2.97 [0.12, 72.18]

23.4 ideation ‐ homicidal

1

217

Risk Ratio (M‐H, Random, 95% CI)

4.95 [0.24, 102.01]

23.5 ideation ‐ suicidal

2

429

Risk Ratio (M‐H, Random, 95% CI)

1.05 [0.15, 7.06]

24 Adverse effects: 2a. Specific ‐ any adverse effect ‐ short term Show forest plot

2

429

Risk Ratio (M‐H, Random, 95% CI)

1.19 [1.02, 1.38]

25 Adverse effects: 2b. Specific ‐ cardiovascular ‐ short term Show forest plot

2

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

25.1 chest pain

2

429

Risk Ratio (M‐H, Random, 95% CI)

1.68 [0.18, 15.99]

25.2 electrocardiogram abnormal

1

212

Risk Ratio (M‐H, Random, 95% CI)

3.00 [0.12, 72.82]

25.3 hypertension

1

212

Risk Ratio (M‐H, Random, 95% CI)

2.50 [0.50, 12.60]

25.4 tachycardia

1

212

Risk Ratio (M‐H, Random, 95% CI)

0.33 [0.01, 8.09]

26 Adverse effects: 2c. Specific ‐ dermatological ‐ short term Show forest plot

3

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

26.27 hair loss

1

36

Risk Ratio (M‐H, Random, 95% CI)

3.00 [0.13, 69.09]

26.34 itching

1

36

Risk Ratio (M‐H, Random, 95% CI)

4.0 [0.49, 32.39]

26.45 rash

3

465

Risk Ratio (M‐H, Random, 95% CI)

0.74 [0.24, 2.28]

27 Adverse effects: 2d. Specific ‐ gastrointestinal ‐ short term Show forest plot

3

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

27.1 constipation

1

212

Risk Ratio (M‐H, Random, 95% CI)

0.33 [0.04, 3.15]

27.2 decreased appetite

1

217

Risk Ratio (M‐H, Random, 95% CI)

0.11 [0.01, 2.02]

27.3 diarrhea

3

465

Risk Ratio (M‐H, Random, 95% CI)

1.56 [0.39, 6.16]

27.4 dyspepsia

1

212

Risk Ratio (M‐H, Random, 95% CI)

4.0 [0.45, 35.20]

27.5 nausea

3

465

Risk Ratio (M‐H, Random, 95% CI)

2.26 [1.05, 4.88]

27.6 vomiting

2

253

Risk Ratio (M‐H, Random, 95% CI)

3.17 [0.77, 13.02]

28 Adverse effects: 2e. Specific ‐ metabolic parameters ‐ short term Show forest plot

2

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

28.1 alanine aminotransferase increase

1

217

Risk Ratio (M‐H, Random, 95% CI)

2.97 [0.12, 72.18]

28.2 aspartate aminotransferase

1

217

Risk Ratio (M‐H, Random, 95% CI)

2.97 [0.12, 72.18]

28.3 blood creatine phosphokinase

1

212

Risk Ratio (M‐H, Random, 95% CI)

0.33 [0.01, 8.09]

28.4 blood glucose increase

1

212

Risk Ratio (M‐H, Random, 95% CI)

1.5 [0.26, 8.80]

29 Adverse effects: 2f. Specific ‐ neurological ‐ short term Show forest plot

3

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

29.1 ataxia

1

36

Risk Ratio (M‐H, Random, 95% CI)

5.00 [0.26, 97.37]

29.2 blurred vision

1

36

Risk Ratio (M‐H, Random, 95% CI)

2.0 [0.20, 20.15]

29.3 dizziness

3

465

Risk Ratio (M‐H, Random, 95% CI)

1.17 [0.51, 2.70]

29.4 headache

3

465

Risk Ratio (M‐H, Random, 95% CI)

1.36 [0.88, 2.08]

29.5 loss of consciousness

1

212

Risk Ratio (M‐H, Random, 95% CI)

5.0 [0.24, 102.92]

29.6 paraesthesia

1

212

Risk Ratio (M‐H, Random, 95% CI)

3.00 [0.12, 72.82]

29.7 hypoaesthesia

1

212

Risk Ratio (M‐H, Random, 95% CI)

7.00 [0.37, 133.88]

29.8 tremor

1

217

Risk Ratio (M‐H, Random, 95% CI)

4.95 [0.59, 41.71]

30 Adverse effects: 2g. Specific ‐ psychiatric ‐ short term Show forest plot

2

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

30.1 aggression

1

217

Risk Ratio (M‐H, Random, 95% CI)

2.97 [0.12, 72.18]

30.2 agitation

1

212

Risk Ratio (M‐H, Random, 95% CI)

0.5 [0.09, 2.67]

30.3 anxiety

2

429

Risk Ratio (M‐H, Random, 95% CI)

0.73 [0.09, 5.76]

30.4 crying

1

212

Risk Ratio (M‐H, Random, 95% CI)

0.33 [0.01, 8.09]

30.5 hallucination, auditory

1

217

Risk Ratio (M‐H, Random, 95% CI)

10.90 [0.61, 194.74]

30.6 insomnia

2

429

Risk Ratio (M‐H, Random, 95% CI)

2.02 [0.04, 96.25]

30.7 paranoia

2

429

Risk Ratio (M‐H, Random, 95% CI)

1.99 [0.37, 10.75]

30.8 somnolence

2

429

Risk Ratio (M‐H, Random, 95% CI)

1.21 [0.51, 2.87]

31 Adverse effects: 2h. Specific ‐ respiratory ‐ short term Show forest plot

1

424

Risk Ratio (M‐H, Fixed, 95% CI)

3.0 [0.48, 18.89]

31.1 cough

1

212

Risk Ratio (M‐H, Fixed, 95% CI)

7.0 [0.37, 133.88]

31.2 influenza

1

212

Risk Ratio (M‐H, Fixed, 95% CI)

1.0 [0.06, 15.78]

32 Adverse effects: 2i. Specific ‐ others ‐ short term Show forest plot

2

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

32.1 abnormal dreams

1

217

Risk Ratio (M‐H, Random, 95% CI)

0.33 [0.01, 8.02]

32.2 asthenia

1

217

Risk Ratio (M‐H, Random, 95% CI)

0.33 [0.01, 8.02]

32.3 back pain

1

217

Risk Ratio (M‐H, Random, 95% CI)

0.99 [0.30, 3.33]

32.4 dry mouth

1

212

Risk Ratio (M‐H, Random, 95% CI)

1.0 [0.21, 4.84]

32.5 fatigue

1

217

Risk Ratio (M‐H, Random, 95% CI)

1.39 [0.45, 4.24]

32.6 lymphadenopathy

2

429

Risk Ratio (M‐H, Random, 95% CI)

2.99 [0.31, 28.48]

32.7 urine abnormality

1

212

Risk Ratio (M‐H, Random, 95% CI)

3.00 [0.12, 72.82]

32.8 weight increase

1

212

Risk Ratio (M‐H, Random, 95% CI)

3.00 [0.12, 72.82]

33 Adverse effects: 3. Events ‐ co‐incident with trial ‐ short term Show forest plot

2

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

33.1 abscess

1

212

Risk Ratio (M‐H, Random, 95% CI)

3.00 [0.12, 72.82]

33.2 arthropod bite

1

212

Risk Ratio (M‐H, Random, 95% CI)

0.33 [0.01, 8.09]

33.3 endometrial cancer

1

212

Risk Ratio (M‐H, Random, 95% CI)

3.00 [0.12, 72.82]

33.5 joint injury

1

217

Risk Ratio (M‐H, Random, 95% CI)

2.97 [0.12, 72.18]

33.6 local swelling

1

217

Risk Ratio (M‐H, Random, 95% CI)

2.97 [0.12, 72.18]

33.7 nasopharyngitis

2

429

Risk Ratio (M‐H, Random, 95% CI)

1.42 [0.28, 7.15]

33.8 pharyngolaryngeal pain

1

212

Risk Ratio (M‐H, Random, 95% CI)

3.00 [0.12, 72.82]

33.9 post‐procedural pain

1

217

Risk Ratio (M‐H, Random, 95% CI)

2.97 [0.12, 72.18]

33.10 tooth abscess

1

217

Risk Ratio (M‐H, Random, 95% CI)

2.97 [0.12, 72.18]

33.11 toothache

1

217

Risk Ratio (M‐H, Random, 95% CI)

0.40 [0.08, 2.00]

33.12 upper respiratory tract infection

2

429

Risk Ratio (M‐H, Random, 95% CI)

1.05 [0.22, 4.94]

34 Adverse effects: 4a. Movement disorders ‐ average endpoint score (ESRS, high = poor, data skewed) Show forest plot

Other data

No numeric data

35 Adverse effects: 4b. Movement disorders ‐ average dose (biperiden, mg, high = poor, data skewed) Show forest plot

Other data

No numeric data
Figuras y tablas -
Comparison 1. ADJUNCTIVE LAMOTRIGINE vs ADJUNCTIVE PLACEBO
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