AD/HD-aikusten puolesta

Kela on perustellut metyylifenidaattilääkityksen peruskorvattavuuden eväämistä sillä, ettei metyylifenidaatin 1) turvallisuudesta ja 2) tehokkuudesta ole näyttöä. Aivan.. Tässä kuitenkin muutama niistä lukemattomista kansainvälisistä, korkeatasoisista tutkimuksista, jotka ovat osoittaneet metyylifenidaatin 1) tehokkuuden ja 2) turvallisúuden aikuisiän ADHD:n hoidossa:

1. Biological Psychiatry (Volume 57, Issue 5, 1 March 2005, Pages 456-463)

"A large, double-blind, randomized clinical trial of methylphenidate in the treatment of adults with attention-deficit/hyperactivity disorder"

Thomas Spencera, Joseph Biedermana, Timothy Wilensa, Robert Doylea, Craig Surmana, Jefferson Princea, Eric Micka, Megan Aleardia, Kathleen Herziga, and Stephen Faraoneb

Background
The few controlled studies of methylphenidate (MPH) in adults with attention deficit/hyperactivity disorder (ADHD) have reported equivocal results. A previous, pilot study by our group suggested that these results were due to inadequate dosing.

Method
We conducted a randomized, 6-week, placebo-controlled, parallel study of MPH in 146 adult patients with DSM-IV ADHD using standardized instruments for diagnosis, separate assessments of ADHD, depressive and anxiety symptoms, and a robust average oral daily dose of 1.1 mg/kg/day.

Results
We found a marked therapeutic response for the MPH treatment of ADHD symptoms that exceeded the placebo response (76% vs. 19%). Treatment was safe and well tolerated. Response to MPH was independent of socioeconomic status, gender, and lifetime history of psychiatric comorbidity.

Conclusions
These results confirm that robust doses of MPH are effective in the treatment of adult ADHD.

2. Psychol Med. (2004 Aug;34(6):973-82)

"Efficacy and safety of methylphenidate in 45 adults with attention-deficit/hyperactivity disorder. A randomized placebo-controlled double-blind cross-over trial"

Kooij JJ, Burger H, Boonstra AM, Van der Linden PD, Kalma LE, & Buitelaar JK

BACKGROUND
Data on the efficacy and safety of methylphenidate in adults with attention deficit/ hyperactivity disorder (ADHD) are lacking in Europe. This study was undertaken to report on the efficacy and safety of methylphenidate in an adult out-patient population with ADHD, and to compare results with US data.

METHOD
A double-blind randomized cross-over trial comparing methylphenidate and placebo in 45 adults with ADHD with childhood onset was performed in a dose-titration design. Methylphenidate was titrated from 0.5 mg/kg per day in week 1 up to 1.0 mg/kg per day in week 3.

RESULTS
Response rates using methylphenidate varied between 38 and 51%, and using placebo between 7 and 18% (p<0.05), depending on outcome measure used. Although the overall percentage of subjects having any side effect on both methylphenidate and placebo was rather high, side effects on methylphenidate over and above those on placebo were few and mild.

CONCLUSIONS
Methylphenidate proves to be an effective and well tolerated treatment for symptoms of ADHD in adults in the short term. Future research should study the long-term response and clarify the impact of gender, co-morbidity, socio-economic status and IQ on response rates in adults with ADHD.

3. (UUSI!!) Brain Research (Volume 1381, 24 March 2011, Pages 159-166)

"Methylphenidate normalizes emotional processing in adult patients with attention-deficit/hyperactivity disorder: Preliminary findings"

Annette Conzelmanna, Eva Woidicha, Ronald F. Muchaa, Peter Weyersa, Christian P. Jacobb, Klaus-Peter Leschb, C, & Paul Paulia

Abstract
Emotional–motivational dysfunctions may significantly contribute to symptoms of attention-deficit/hyperactivity disorder (ADHD). Hyperactive–impulsive symptoms and sensation seeking could be the result of a search for reinforcers, and cognitive dysfunctions might be due to a low motivational drive. Emotional-motivational dysfunctions could also explain social dysfunctions in ADHD patients because they may lead to misinterpretations of emotional and social clues. Since methylphenidate (MPH) is the first choice as a pharmacological treatment in ADHD, we examined its influence on dysfunctional emotional processes. 13 adult ADHD patients were examined twice, without and after intake of MPH according to their personal medication regimen. The affect-modulated startle paradigm was used to assess physiological (affect-modulated startle response) and subjective (valence and arousal ratings) responses to pleasant, neutral and unpleasant visual stimuli. Healthy controls displayed affective startle modulation as expected, with startle attenuation and potentiation while watching pleasant and unpleasant pictures, respectively. In contrast, unmedicated ADHD patients displayed deficient responses to pleasant stimuli; no startle attenuation during the exposure to pleasant pictures was observed. However, MPH reinstated a normal affective startle modulation, as indicated by attenuation and potentiation associated with pleasant and unpleasant pictures, respectively. Valence and arousal ratings of patients were not affected by MPH.

The data suggest that MPH as first choice treatment in ADHD has a positive impact on emotional processes in adult ADHD patients and points to the clinical relevance of emotional-dysfunctions in ADHD.

4. Biological Psychiatry (Volume 59, Issue 9, 1 May 2006, Pages 829-835)

"A Randomized, Placebo-Controlled Trial of OROS Methylphenidate in Adults with Attention-Deficit/Hyperactivity Disorder"

Joseph Biedermana, b, Eric Micka, b, Craig Surmana, b, Robert Doylea, b, Paul Hammernessa, b, Theresa Harpolda, b, Stephanie Dunkelb, Meghan Doughertyb, Megan Aleardib, & Thomas Spencera, b

Background
The objective of this study was to evaluate the safety and efficacy of once-daily OROS methylphenidate (MPH) in the treatment of adults with DSM-IV attention-deficit/hyperactivity disorder (ADHD).

Methods
We conducted a randomized, 6-week, placebo-controlled, parallel-design study of OROS MPH in 141 adult subjects with DSM-IV ADHD, using standardized instruments for diagnosis. OROS MPH or placebo was initiated at 36 mg/day and titrated to optimal response, depending on efficacy and tolerability, up to 1.3 mg/kg/day.

Results
Treatment with OROS MPH was associated with clinically and statistically significant reductions in DSM-IV symptoms of inattention and hyperactivity/impulsivity relative to subjects treated with placebo. At endpoint, 66% of subjects (n = 44) receiving OROS MPH and 39% of subjects (n = 23) receiving placebo attained our a priori definition of response of much or very much improved on the Clinical Global Impression–Improvement scale plus a >30% reduction in Adult ADHD Investigator System Report Scale score. OROS MPH was associated with small but statistically significant increases in systolic blood pressure (3.5 ± 11.8 mm Hg), diastolic blood pressure (4.0 ± 8.5 mm Hg), and heart rate (4.5 ± 10.5 bpm).

Conclusions
These results show that treatment with OROS MPH in daily doses of up to 1.3 mg/kg/day was effective in the treatment of adults with ADHD. Because of the potential for increases in blood pressure and heart rate, subjects receiving treatment with MPH should be monitored for changes in blood pressure parameters during treatment.

5. (HUOM: yksi artikkelin kirjoittajista on mm. OYS:ssa toimiva ADHD-asiantuntija Asko Niemelä)

Biological Psychiatry (Volume 63, Issue 10, 15 May 2008, Pages 981-989)

"A Randomized, Placebo-Controlled Trial of Three Fixed Dosages of Prolonged-Release OROS Methylphenidate in Adults with Attention-Deficit/Hyperactivity Disorder"

Rossella Medoria, J. Antoni Ramos-Quirogab, c, Miguel Casasb, c, J.J.S. Kooijd, Asko Niemeläe, Götz-Erik Trottf, Emma Leeg, & Jan K. Buitelaarh

Background
There is increasing recognition of attention-deficit/hyperactivity disorder (ADHD) in adults and the need to evaluate efficacy and safety of methylphenidate treatment in these patients.

Methods
In this double-blind trial, 401 adults with ADHD (218 men; 18–63 years) were randomly assigned to receive prolonged-release osmotic release oral system (OROS) methylphenidate (18 mg, 36 mg, or 72 mg/day) or placebo for 5 weeks. Primary outcome was change in total score on Conners' Adult ADHD Rating Scale (CAARS: investigator-rated) at end point compared with baseline. Adverse events, vital signs, and laboratory parameters were assessed.

Results
Treatment with 18-mg, 36-mg, and 72-mg/day prolonged-release methylphenidate, compared with placebo, was associated with significantly larger improvement in CAARS total symptom score from baseline to end point than placebo: mean change −10.6 (p = .01), −11.5 (p = .01), and −13.7 (p < .001) versus −7.6, respectively. Responders (≥30% decrease) were 50.5%, 48.5%, and 59.6% versus 27.4% (p < .001). Other efficacy measures also showed improvements. Incidence of adverse events was 75%, 76%, and 82% in 18-mg, 36-mg, and 72-mg/day groups, respectively, and 66% in placebo; most frequent included decreased appetite (25% methylphenidate; 7% placebo) and headache (21% methylphenidate; 18% placebo). In methylphenidate-treated patients, 4.3% discontinued due to adverse event; one serious adverse event was possibly related to study drug. Blood pressure and pulse increased at week 1 and then remained stable through week 5.

Conclusions
!!!!! Prolonged-release methylphenidate is an effective treatment of ADHD in adults, with a safety profile consistent with methylphenidate use in pediatrics.

6. Biological Psychiatry (Volume 65, Issue 7, 1 April 2009, Pages 614-619)

"Methylphenidate Restores Link Between Stop-Signal Sensory Impact and Successful Stopping in Adults with Attention-Deficit/Hyperactivity Disorder"

Carin C.E. Overtooma, B.C. Evelijne M. Bekkerb, Maurits W. van der Molena, Marinus N. Verbatenb, J.J. Sandra Kooije, Jan K. Buitelaarf, & J. Leon Kenemansb

Background
The ability to revise one's action plans, as reflected in so-called stopping performance, is of fundamental importance to adaptive behavior. Previous studies in children and adults with attention-deficit/hyperactivity disorder (ADHD) have revealed impaired stopping, which improved after the administration of methylphenidate (MPH). Event-related brain potentials revealed that one crucial mechanism in adequate stopping is the link between the cortical areas that process the signal to stop and the motor system (stop N1). This stop N1 was severely compromised in adults with ADHD. The present study investigates whether methylphenidate can restore the stop N1, in addition to improving stopping performance. The acute effect of a serotonergic reuptake inhibition on these parameters was also assessed.

Methods
Twelve adult combined-type ADHD patients received either placebo, MPH .4 mg/kg or .6 mg/kg, or 20 mg paroxetine in a double-blind, randomized, within-subjects design.

Results
The .6 mg/kg dose of methylphenidate improved stopping performance, whereas it did not affect go reaction time (RT). It also restored the stop N1 that was absent under placebo. Methylphenidate reduced a later stop-related potential, the stop P3, which may reflect monitoring of failed stops. Paroxetine had no effect on stopping performance or on stop N1, but it reduced stop P3.

Conclusions
A .6 mg/kg dose of methylphenidate improves stopping performance and directly targets a stop-related brain mechanism that has been reported before to be compromised in a group of ADHD patients. This mechanism was not influenced by acute serotonergic reuptake inhibition.


7. Biological Psychiatry (Volume 63, Issue 10, 15 May 2008, Pages 981-989)

"A Randomized, Placebo-Controlled Trial of Three Fixed Dosages of Prolonged-Release OROS Methylphenidate in Adults with Attention-Deficit/Hyperactivity Disorder"

Rossella Medoria, J. Antoni Ramos-Quirogab, c, Miguel Casasb, c, J.J.S. Kooijd, Asko Niemelä, Götz-Erik Trottf, Emma Leeg, & Jan K. Buitelaarh

Background
There is increasing recognition of attention-deficit/hyperactivity disorder (ADHD) in adults and the need to evaluate efficacy and safety of methylphenidate treatment in these patients.

Methods
In this double-blind trial, 401 adults with ADHD (218 men; 18–63 years) were randomly assigned to receive prolonged-release osmotic release oral system (OROS) methylphenidate (18 mg, 36 mg, or 72 mg/day) or placebo for 5 weeks. Primary outcome was change in total score on Conners' Adult ADHD Rating Scale (CAARS: investigator-rated) at end point compared with baseline. Adverse events, vital signs, and laboratory parameters were assessed.

Results
Treatment with 18-mg, 36-mg, and 72-mg/day prolonged-release methylphenidate, compared with placebo, was associated with significantly larger improvement in CAARS total symptom score from baseline to end point than placebo: mean change −10.6 (p = .01), −11.5 (p = .01), and −13.7 (p < .001) versus −7.6, respectively. Responders (≥30% decrease) were 50.5%, 48.5%, and 59.6% versus 27.4% (p < .001). Other efficacy measures also showed improvements. Incidence of adverse events was 75%, 76%, and 82% in 18-mg, 36-mg, and 72-mg/day groups, respectively, and 66% in placebo; most frequent included decreased appetite (25% methylphenidate; 7% placebo) and headache (21% methylphenidate; 18% placebo). In methylphenidate-treated patients, 4.3% discontinued due to adverse event; one serious adverse event was possibly related to study drug. Blood pressure and pulse increased at week 1 and then remained stable through week 5.

Conclusions
Prolonged-release methylphenidate is an effective treatment of ADHD in adults, with a safety profile consistent with methylphenidate use in pediatrics.