Table 2.
Overview of behavioral changes observed in persons treated with methylphenidate
| Study | Limit for symptoms (%) | Abnormal behavior | Accidental injury | Agitation | Aggression | Anxiety | Depression | Depressed mood |
|---|---|---|---|---|---|---|---|---|
| Adler et al51 | *1) | – | – | 5% | – | 12% | – | – |
| Adler et al31 | 10 | – | – | – | – | 13% | – | – |
| Bejerot et al52 | – | – | – | – | – | – | – | – |
| Bron et al15 | – | – | – | – | – | – | – | – |
| Buitelaar et al32 | 2 | – | – | – | – | 5% | – | 4% |
| Buitelaar et al65 | 4–5 *2) | – | – | – | – | 2% | – | 5% |
| Casas et al33 | 5 | – | – | 8% | – | 9% | – | 6% |
| Fredriksen et al53 | – | – | – | Yes | Yes | Yes | – | – |
| Huss et al54,55 | 5 | – | – | – | – | 5% | – | – |
| Kooij et al45 | – | – | – | – | – | – | – | – |
| Valdizán-Usón et al62 | – | – | – | – | – | – | – | – |
| Amiri et al23 | – | – | – | – | – | 13% | – | – |
| Arabgol et al22 | – | – | – | – | – | – | – | – |
| Barbaresi et al18 | – | – | – | – | – | – | – | – |
| Barkley et al46 | – | – | – | – | – | 58% | – | – |
| Biederman et al21 | – | – | – | – | – | Yes | – | – |
| Cherland and Fitzpatrick63 | – | – | – | – | – | – | – | – |
| Döpfner et al56 | – | – | – | – | 3% | – | 1% | 1% |
| Efron et al47 | – | – | – | – | – | 61% | – | – |
| Findling et al24 | 3 | 3% | – | – | 3% | – | – | – |
| Garg et al57 | – | – | – | – | – | – | – | – |
| Gau et al27 | – | – | – | – | – | 31% | – | – |
| Ghuman et al16 | – | – | – | 11% | – | 3% | – | – |
| Greenhill et al26 | 2 | – | – | – | – | – | – | – |
| Haertling et al58 | – | – | – | 1% | 1% | – | 1% | – |
| Karabekiroglu et al59 | – | – | – | – | – | – | – | – |
| Kemner et al28 | 1 | 1% | – | – | 1% | – | – | – |
| Khajehpiri et al60 | – | – | – | 36% | – | – | – | – |
| Kratochvil et al30 | 5 | 5% | 12% | – | – | – | 5% | – |
| Lee et al48 | – | – | – | – | – | 38% | – | – |
| Maayan et al17 | – | – | – | – | 9% | – | – | – |
| MTA group34–39 | – | – | – | – | – | – | – | – |
| Newcorn et al25 | 5 | – | – | – | – | – | – | – |
| PATS group40–42 | *3) | – | – | – | 4% | 3% | – | – |
| Pelham et al49 | 2 | – | 4% | – | – | – | – | – |
| Smith et al19 | – | – | – | – | – | – | – | – |
| Ramtvedt et al64 | – | – | – | – | – | 30% | – | – |
| Robb et al61 | 5 | – | – | – | 6% | – | – | – |
| Silva et al14 | – | – | – | – | – | – | – | – |
| Steele et al66 | 10 | – | – | 11% | – | – | – | – |
| Stein et al50 | – | – | – | – | – | 55% | – | – |
| Swanson et al29 | 2 | – | – | – | – | – | – | – |
| Wigal et al44 | 5 | – | – | – | – | – | – | – |
| Zarinara et al43 | – | – | – | – | – | – | – | – |
| Total | – | 1%–5% | 4%–12% | 1%–36% | 1%–9% | 2%–61% | 1%–5% | 1%–6% |
| Placebo in total | – | 0%–4% | 0%–3% | 0%–1% | 0%–5% | 1%–58% | – | 1%–5% |
| Adult | – | – | – | 5%–8% | – | 2%–13% | – | 4%–6% |
| Placebo adult | – | – | – | 1% | – | 1%–7% | – | 1%–5% |
| Child | – | 1%–5% | 4%–12% | 1%–36% | 1%–9% | 3%–61% | 1%–5% | 1% |
| Placebo child | – | 0%–4% | 0%–3% | – | 0%–5% | 1%–58% | – | – |
| Study | Disinterested in others | Dizziness | Drowsiness | Emotional lability | Euphoria | Feeling jittery | Irritability | Mood alteration | Nail biting |
|---|---|---|---|---|---|---|---|---|---|
| Adler et al51 | – | – | – | – | – | 13% | 8% | – | – |
| Adler et al31 | – | – | – | – | – | – | 10% | – | – |
| Bejerot et al52 | – | 17% | – | – | – | – | – | 10% | – |
| Bron et al15 | – | – | – | – | – | – | – | – | – |
| Buitelaar et al32 | – | 8% | – | – | – | – | 5% | – | – |
| Buitelaar et al65 | – | – | – | – | – | – | 4% | – | – |
| Casas et al33 | – | 12% | – | – | – | – | 5% | – | – |
| Fredriksen et al53 | – | – | – | Yes | – | – | – | – | – |
| Huss et al54,55 | – | 6% | – | – | – | – | 6% | – | – |
| Kooij et al45 | – | 16% | – | – | – | 15% | – | – | |
| Valdizán-Usón et al62 | – | – | – | – | – | – | – | – | – |
| Amiri et al23 | – | – | – | – | – | – | 20% | – | – |
| Arabgol et al22 | – | – | 0 | – | – | – | 6% | – | – |
| Barbaresi et al18 | – | – | – | – | – | – | – | – | – |
| Barkley et al46 | 43% | 10% | 25% | – | 43% | – | 66% | – | 29% |
| Biederman et al21 | – | – | Yes | Yes | – | – | – | – | – |
| Cherland and | – | – | – | – | – | – | – | – | – |
| Fitzpatrick63 | |||||||||
| Döpfner et al56 | – | – | – | – | – | – | – | – | – |
| Efron et al47 | 31% | 12% | 18% | – | 28% | – | 80% | – | 45% |
| Findling et al24 | – | – | – | 3% | – | – | 3% | – | – |
| Garg et al57 | – | – | 3% | – | – | – | 6% | – | – |
| Gau et al27 | 40% | – | 25% | – | 28% | – | 21% | – | 25% |
| Ghuman et al16 | – | – | 18% | 29% | – | – | 29% | – | – |
| Greenhill et al26 | – | – | – | 3% | – | – | 3% | – | – |
| Haertling et al58 | – | 1% | – | 1% | – | – | – | 1% | – |
| Karabekiroglu et al59 | – | – | – | – | – | – | – | – | – |
| Kemner et al28 | – | 1% | – | 1% | – | – | 1% | 1% | – |
| Khajehpiri et al60 | – | – | – | – | – | – | 57% | – | – |
| Kratochvil et al30 | – | – | 0 | 5% | – | – | – | – | – |
| Lee et al48 | 17% | 6% | 16% | – | 25% | – | 64% | – | 30% |
| Maayan et al17 | – | – | 9% | 18% | – | – | – | – | – |
| MTA group34–39 | – | – | – | – | – | – | – | – | – |
| Newcorn et al25 | – | – | – | – | – | – | 6% | – | – |
| PATS group40–42 | – | – | Yes | 15% | – | – | 8% | 7% | – |
| Pelham et al49 | – | 3% | – | – | – | – | – | – | – |
| Smith et al19 | – | – | – | – | – | – | – | – | – |
| Ramtvedt et al64 | 21% | 18% | 32% | – | 18% | – | 65% | – | – |
| Robb et al61 | – | 6% | – | 26% | – | – | 13% | – | – |
| Silva et al14 | – | – | – | – | – | – | 0 | – | – |
| Steele et al66 | – | – | – | 13% | – | – | – | – | – |
| Stein et al50 | 34% | 11% | 28% | – | 16% | – | 71% | – | 22% |
| Swanson et al29 | – | – | – | – | – | – | 1% | – | – |
| Wigal et al44 | – | 9% | – | – | – | – | – | – | – |
| Zarinara et al43 | – | – | – | – | – | – | – | – | – |
| Total | 17%–41% | 1%–18% | 0%–32% | 1%–29% | 16%–43% | 13% | 0%–80% | 1%–10% | 22%–45% |
| Placebo in total | 17%–36% | 0%–15% | 8%–53% | 0%–11% | 25%–45% | 2% | 1%–80% | 6% | 15%–29% |
| Adult | – | 6%–17% | 0%–32% | – | – | 13% | 4%–15% | 10% | – |
| Placebo, adult | – | 2%–7% | 8%–53% | – | – | 2% | 1%–23% | – | – |
| Child | 17%–41% | 1%–18% | 0%–32% | 1%–29% | 16%–43% | – | 0%–80% | 1%–7% | 22%–45% |
| Placebo, child | 17%–36% | 0%–15% | 8%–53% | 0%–11% | 25%–45% | – | 1%–80% | 6% | 15%–29% |
| Study | Nervousness | Nightmares | Prone to crying | Psychomotor hyperactivity | Restlessness | Sadness | Staring | Talks less | Tics |
|---|---|---|---|---|---|---|---|---|---|
| Adler et al51 | – | – | – | 5% | – | – | – | – | – |
| Adler et al31 | – | – | – | – | – | – | – | – | – |
| Bejerot et al52 | 12% | – | – | – | – | – | – | – | 1% |
| Bron et al15 | 23% | – | – | – | – | – | – | – | – |
| Buitelaar et al32 | 3% | – | – | – | 5% | – | – | – | – |
| Buitelaar et al65 | – | – | – | – | 7% | – | – | – | – |
| Casas et al33 | – | – | – | – | 9% | – | – | – | – |
| Fredriksen et al53 | – | – | – | – | – | – | – | – | Yes |
| Huss et al54,55 | – | – | – | – | 4% | – | – | – | – |
| Kooij et al45 | – | – | – | – | – | – | – | – | 7% |
| Valdizán-Usón et al62 | – | – | – | – | – | – | – | – | – |
| Amiri et al23 | – | – | – | – | – | 20% | – | – | – |
| Arabgol et al22 | – | – | – | – | – | – | – | – | – |
| Barbaresi et al18 | – | – | – | – | – | – | – | – | – |
| Barkley et al46 | – | 21% | 59% | 28% | – | 48% | 57% | 42% | – |
| Biederman et al21 | – | – | – | – | – | – | – | – | – |
| Cherland and | – | – | – | – | – | – | – | – | – |
| Fitzpatrick63 | |||||||||
| Döpfner et al56 | – | – | – | – | – | 17% | – | – | 12% |
| Efron et al47 | – | 21% | 71% | – | – | 56% | 62% | 28% | 28% |
| Findling et al24 | – | – | – | – | – | – | – | – | 0 |
| Garg et al57 | – | – | – | – | – | – | – | – | – |
| Gau et al27 | – | 25% | 47% | – | – | – | 31% | 31% | 18% |
| Ghuman et al16 | – | – | 29% | 3% | – | – | – | – | – |
| Greenhill et al26 | – | – | – | – | – | – | – | – | – |
| Haertling et al58 | – | – | – | – | – | – | – | – | – |
| Karabekiroglu et al59 | – | – | – | – | – | – | – | – | – |
| Kemner et al28 | – | – | 1% | – | – | – | – | – | – |
| Khajehpiri et al60 | – | 24% | – | – | – | – | – | – | 35% |
| Kratochvil et al30 | 10% | – | – | – | – | – | – | – | – |
| Lee et al48 | – | 13% | 49% | – | – | 38% | 35% | 27% | 17% |
| Maayan et al17 | – | – | – | – | – | – | – | – | – |
| MTA group34–39 | – | – | – | – | – | – | – | – | – |
| Newcorn et al25 | – | – | – | – | – | – | – | – | – |
| PATS group40–42 | – | – | – | – | – | – | – | – | – |
| Pelham et al49 | – | – | – | 5% | – | – | – | – | – |
| Smith et al19 | – | – | – | – | – | – | – | – | – |
| Ramtvedt et al64 | – | 9% | 65% | – | – | 41% | 21% | 29% | 15% |
| Robb et al61 | – | – | – | – | – | – | – | – | – |
| Silva et al14 | – | – | – | – | – | – | – | – | – |
| Steele et al66 | – | 13% | – | – | – | – | – | – | – |
| Stein et al50 | – | 17% | 54% | – | – | 47% | 54% | 32% | 17% |
| Swanson et al29 | – | – | – | – | – | – | – | – | – |
| Wigal et al44 | – | – | – | – | – | – | – | – | – |
| Zarinara et al43 | – | – | – | – | 26% | – | – | – | – |
| Total | 3%–23% | 9%–25% | 1%–71% | 3%–28% | 4%–26% | 0%–56% | 21%–62% | 27%–42% | 0%–35% |
| Placebo in total | 1% | 12%–20% | 38%–49% | 0%–7% | 0%–4% | 31%–50% | 30%–68% | 15%–38% | 2%–30% |
| Adult | 3%–23% | – | – | 5% | 4%–9% | – | – | – | 1% |
| Placebo, adult | 1% | – | – | 7% | 0%–4% | – | – | – | 2% |
| Child | 10% | 9%–25% | 1%–71% | 3%–28% | 26% | 0%–47% | 21%–62% | 27%–42% | 0%–35% |
| Placebo, child | – | 12%–20% | 38%–49% | – | – | 31%–50% | 30%–68% | 15%–38% | 4%–30% |
Notes:
*1)
“most frequently recorded”.
*2)
5 (recorded in open-label), 4 (recorded in withdrawal);
*3)
15 most frequently recorded adverse events.