Hallucinations and other psychotic symptoms in response to methylphenidate in children and adolescents with attention-deficit/hyperactivity disorder: a Cochrane systematic review with meta-analysis and trial sequential analysis#
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Article Category: review
Online veröffentlicht: 10. Juli 2018
Seitenbereich: 52 - 71
DOI: https://doi.org/10.21307/sjcapp-2018-003
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© 2018 Erica Ramstad et al., published by Sciendo
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
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Characteristics of included randomized clinical trials
| Study ID, country | Study design | N | Age range Mean (SD) (years) | Male [n (%)] | MPH-naïve [n (%)] | MPH type, mean daily dose Dosage regimen | Time of MPH intervention | Mode of assessment | Type and number of psychotic events |
|---|---|---|---|---|---|---|---|---|---|
| Becker 2016/Froehlich 2015, USA | Cross-over | 163 | 7-11 | 117 (72) | 163 (100) | MPH-OROS | 3 weeks | Pittsburgh Side Effect Rating Scale, Parent rated | Hallucination Placebo: n=0/163 |
| Buitelaar 1996, The Netherlands | Cross-over | 52 | 6-13 | 46 (88) | 52 (100) | MPH-IR, 20 mg | 4 weeks | Modified Stimulant Drug Side Effects Rating scale, Parent rated | Interim analysis Hallucination: n=1 |
| Childress 2009, NCT-00301236, USA | Parallel | 253 | 6-12 | 163 (64) | 175 (69) | MPH-ER, 10/20/30 mg (3 parallel groups) | 5 weeks | Regular monitoring of serious adverse events | Tactile hallucination: n=1 (30 mg) |
| Palumbo 2008/Daviss 2008, NCT-00031395, USA | Parallel | 122 | 7-12 | 98 (80) | 57 (47) | MPH-IR, 30.2 mg 1 to 3 times daily (in the morning, noon and at 4 p.m.) | 12 weeks | Pittsburgh Side Effect Rating Scale, Parent and teacher rated. Spontaneous self-reports. | Groups without co-intervention hallucination: n=0/59 |
| Green 2011, NCT-00768820, Israel | Parallel | 34 | 5-20 | 20 (59) | 21 (62) | MPH-IR, 15.7 mg 1 dose | 1 day | Spontaneous reports | Psychotic symptoms: n=0 |
| Pelham 1999, USA, Summer Treatment Program 1988 | Cross-over | 21 | 6-12 | 19 (90) | 7 (33) | MPH-IR, 0.9/0.75/0.3 mg/kg 1 to 3 times daily (morning, noon and afternoon at 3:30 p.m.) | 1day×3 (placebo: 2 daysx3) | Pittsburgh Side Effect Rating Scale. Parent, teacher, and counselor rated | Hallucination: n=1 |
| Pelham 2005, USA, Summer Treatment Program | Cross-over | 36 | 6-13 | 33 (92) | 26 (72) | MTS, 0.45/0.9/1.8 mg/h | 1 day×2 | Pittsburgh Side Effect Rating Scale. Parent, teacher, and counselor rated | Hallucination: n=0 |
| Riggs 2011, NCT-00264797, USA | Parallel | 303 | 13-18 16.5 (1.3) | 239 (79) | NA | MPH-OROS, 68 mg | 16 weeks | Systematic assessment of serious adverse events | Psychotic disorder: n=1 |
| Schachar 2008, USA | Cross-over | 18 | 6-15 | 15 | NA | MPH-IR or MPH-ER, 31.2 mg 1 to 2 times daily (morning- and lunch-time dose) | 1 week | Spontaneous reporting | Psychosis: n=1 |
| Waxmonsky 2008, NCT-00050622, USA, Summer Treatment Program | Cross-over | 101 | 5-12 | 82 (81) | NA | MPH-IR, 15/30/54 mg | 1day×3–4×3 | Pittsburgh Side Effect Rating Scale. Staff and parent rated | NA |
Characteristics of included non-randomised studies
| Study ID, country | N | Age range mean (SD) (years) | Male [n (%)] | MPH-naïve [n (%)] | MPH type, mean daily dose Dosage regimen | Time of intervention | Mode of assessment | Type and number of psychotic events |
|---|---|---|---|---|---|---|---|---|
| Ashkenasi 2011, NCT00989950, USA | 26 | 6-12 | 19 | NA | MTS, 10 ➔ max 30 mg (optimal dose) | Titration +4 weeks maintenance | Spontaneous reporting | Withdrawal due to hallucinations n=1 |
| Arnold 2015, TOSCA study, NCT00796302,USA | 168 | 6-12 | 129 | NA | MPH-OROS, ➔ 44.8 mg | 3 weeks titration +6 weeks maintenance | NA | Hallucinations n=0/156 in 3 weeks (0/70 in 9 weeks) |
| Baweja 2016,USA | NA | NA | NA | NA | MPH | 6 weeks | Pittsburgh Side Effects Rating Scale | Hallucinations n=NA |
| Cherland 1999, Canada | 98 | 4-17 | NA | NA | MPH | 21 months | Spontaneous reporting | Psychotic effects n=7/96 |
| Cortese 2015,Italy | 1426 | 6-18 | 1247 | NA | MPH-IR, 18.3 mg | up to 5 years | A structured form including any psychiatric symptomatology | Hallucination n=2 |
| Didoni 2011, Italy | 34 | 6-17 | 28 | 34 (100) | MPH-IR, 39.9 mg 2-3 times daily. | > 1 year | Parents were requested in advance to report any adverse events during follow-up visits | Psychotic symptoms n=0 |
| Elman 1998, Israel | 5 | NA NA (NA) | NA | NA | MPH | NA | NA | n=0 |
| Findling 2009, NCT-00151957, USA | 326 | 6-12 | 212 (65) | ∼ 0 (∼ 0) | MTS, 10➔15➔20➔30 mg | 12 months | Systematic assessment | Psychosis/mania n=3 |
| Green 2011, NCT-00768820, Israel | 16 | 5-20 | NA | 0 (0) | MPH | 6 months | Spontaneous reports | Psychotic symptoms n=0 |
| Lee 2013/NA 2013, Republic of Korea, NCT01060150 | 55 | 12-18 | 43 | NA | MPH-OROS, 45.78 mg | 12 weeks | Adverse event checklist and general questioning | Hallucination n=0/55 |
| 121 | 12-18 | 93 | NA | 54.53 mg | 12 weeks | Adverse event checklist and general questioning | Withdrawal due to hallucinations n=1/121 | |
| MacKenzie 2016, Canada | 141 | 6-21 | 67 | NA | MPH | >12 months | Schizophrenia proneness instrument-child and youth version and structured interview for prodromal syndrome | Psychotic symptoms: Patients, +mph: n=6/NA |
| Man 2016, Hong Kong | 76 | 6-19 | NA | NA | MPH-IR and –ER, NA | Mean: 2.17 years | Psychotic disorder or hallucination diagnostic code in the Clinical Data Analysis and Reporting System | Baseline period (no drug): n=NA Exposed period: n=NA |
| Mohammadi 2004, Iran | 16 | 6-14 | 11 | 16 (100) | MPH | 6 weeks | NA | Hallucination, delusion n=0 |
| Remschmidt 2005/Hoare 2005, UK and Germany | 89 | 6-16 | NA | 0 (0) | MPH-OROS, 18, 36 or 54 mg | 1 year | NA | Delusion n=1 (18 mg) |
| Shyu 2015, Taiwan | ADHD: 73,049 | NA | 58,293 | NA | MPH | 5 months – 12 years | Schizophrenia spectrum disorders based on insurance status, outpatient and hospitalization claims databases | Psychotic disorder: |
| ADHD+MP H: | Schizophrenia: | |||||||
| Su 2015, China | 239 | 6-16 | 203 | NA | MPH-OROS, 18➔ 36 ➔54 mg | 8-week titration phase | Treatment-emergent adverse events were recorded throughout the study | Hallucination n=1 |
| Wilens 2005, USA | 407 | 6-13 | 338 | 0 (0) | MPH-OROS, 35.2➔44.2 mg | 21-24 months | Systematic assessment, parent rated | Withdrawal due to hallucinations n=1 |
Risk of bias in non-randomised studies
| Shyu 2015 | |
|---|---|
| Bias due to confounding | Critical |
| Bias in selection of participants into the study | Moderate |
| Bias in classification of interventions | Moderate |
| Bias due to deviations from intended interventions | Critical |
| Bias due to missing data | Critical |
| Bias in measurement of outcomes | Serious |
| Bias in selection of the reported result | No information |
| Risk of bias judgement | Critical |
Characteristics of included patient reports
| Study ID, country | N | Age, (years) | Sex | MPH-naïve (n) | MPH type, mean daily dose | Time of intervention | Type and number of psychotic events |
|---|---|---|---|---|---|---|---|
| Aguilera-Albesa 2010, Spain | 2 | 6 | F | NA | 50% MPH-IR/50% MPH-ER, 10➔20 mg | 4 days | Hallucinations: n=2 |
| 8 | M | NA | MPH-ER, 18 mg | 2 days | |||
| Coignoux 2009, France | 1 | 14 | M | NA | MPH-ER, 54 mg | 6 months | Psychotic symptoms: n=1 |
| Fernández-Fernández 2011, Spain | 1 | 10 | M | 0 | MPH-ER, 1.2 mg/kg | 1 week | Psychosis: n=1 |
| Goetz 2011, Czech Republic | 1 | 7 | F | 0 | MPH-OROS, 18 mg | 2.5 months | Hallucination: n=1 |
| Gross-Tsur 2004, Israel | 3 | 7 | M | NA | MPH | 1 year | Hallucinations: n=3 |
| 12 | M | NA | MPH | Short period | |||
| 7.5 | M | NA | MPH | Months | |||
| Halevy 2009, Israel | 1 | 8 | M | 1 | MPH | Days | Hallucination: n=1 |
| Herguner 2015, Turkey | 1 | 6 | M | NA | MPH-OROS, 18 mg | 2 months | Hallucination: n=1 |
| Irmak 2014, Turkey | 1 | 9 | M | 1 | MPH | NA | Hallucination: n=1 |
| Porfirio 2011, Italy | 1 | 11 | M | 1 | MPH-IR, 30 mg | 3 years | Hallucination: n=1 |
| Rashid 2007, USA | 1 | 10 | M | 0 | MPH-IR, 20➔30 mg | 2 days | Hallucination: n=1 |
| Shibib 2009, UK | 4 | 14 | F | 1 | MPH-ER, 30 mg | 4 months | Psychosis: n=4 |
| 8 | M | 1 | MPH-IR, 5➔20 mg | 7 days | |||
| 10 | M | 0 | MPH-ER, 36➔54 mg | 3 weeks | |||
| 14 | M | 0 | MPH-ER, 18 mg | 24 hours | |||
| Tomás Vila 2010, Spain | 1 | 10 | M | 0 | 50% MPH-IR/50% MPH-ER, 30 mg | 2 weeks | Hallucination: n=1 |