Effects of Expectation, Medication and Placebo on Objective and Self-rated Performance
Condition: Attention Deficit Hyperactivity Disorder; Substance Use Disorder
MeSH terms: Substance-Related Disorders; Attention Deficit Disorder with Hyperactivity
Study type: Interventional
Phase: Phase 4

Summary: 
      Aim: The purpose of the study is to examine the effects of medication, placebo and
      expectation on objective and self-rated performance of ADHD core signs during the Quantified
      Behavior Test in patients with untreated ADHD and substance Use Disorders.

      Subjects: Participants are 40 consecutive patients remitted to a neuropsychiatric
      investigation at the Dependence Clinic Västmanland, Västerås, Sweden.

      Method: The study is a double-blind, randomized, placebo-controlled, cross-over study. The
      study is taken place during four hours on two investigating days, separated by a 4 days
      wash-out period.

      All patients participate on two occasions: In one session they receive the Methylphenidate
      (MPH) condition, and in the other session they receive the placebo condition. MPH and placebo
      conditions are counterbalanced across subjects such that half of the participants receive MPH
      first, and half receive placebo first. Neither the patient nor the research assistant is
      aware when the participant receive the MPH condition or the placebo condition.

      On each investigating day the participant accomplish Questionnaires (Visual Analogical
      Scales) concerning; (a) expectation, (b) self-rated performance, (c) exhausting exercise, (d)
      perceived help from the pill and (e) self-rated symptoms. In addition the participant
      completed A Quick Test of Cognitive Speed (AQT) and two separate Quantified Behavior Test
      Plus (QbTest) without medication vs MPH/Placebo. QbTest aims to provide objective information
      regarding core-symptoms of ADHD; hyperactivity on the basis of motor-activity measured with
      the camera, and inattention and impulsivity on basis of the CPT-test.
    

Detailed description: 
      Introduction: During the last decade, neuropsychiatric impairments in adults have more often
      been observed. Requests for neuropsychiatric investigations, especially concerning Attention
      Deficit Hyperactivity Disorder (ADHD) has increased. The core ADHD symptoms in adults include
      a frequent and persistent pattern of inattention/distractibility and/or
      hyperactivity/impulsivity (Adler 2004; Adler & Chua 2002; McGough & Barkley 2004). In a
      Swedish study, 22 % of the outpatients in general psychiatric care, were diagnosed with ADHD
      (Nylander et al 2009).

      Individuals with ADHD also have an increased risk for other psychiatric disorders, e.g. major
      depressive episodes, bipolar disorder, anxiety disorders and antisocial personality disorder
      (Rasmussen & Levander 2009; Torgersen, Gjervan & Rasmussen 2006). The co-occurrence of ADHD
      and substance use disorder (SUD) is a prevalent phenomenon that has been demonstrated in
      numerous studies over the past decade (Arias et al 2008; Bernardi et al 2012; van Emmerik-van
      Oortmerssen et al 2012).

      The prevalence of substance abuse in adults with ADHD has been estimated at 50 % and among
      addicts seeking treatment, one third of the patients are identified as probable ADHD, when
      screening instruments have been used (Sullivan & Rodnik-Levin 2001; Ohlmeier et al 2008). The
      National Board of Health and Welfare in Sweden noted that the presence of people with ADHD
      and substance abuse varies between 20 % and 35 % depending on what kind of drugs that have
      been used (Socialstyrelsen 2002).

      Pharmacotherapy, mainly with central stimulant medication, is considered to be the treatment
      of choice for ADHD. In addition, there are patients who request an ADHD diagnosis to obtain
      drug treatment (Harrison, Edwards & Parker 2007).

      Patients' expectation can influence the outcome of a treatment (Bingel et al 2011). Linde et
      al showed that patients with high expectations before the acupuncture treatment, achieved
      better treating result than the patients who had lower expectations of treatment (Linde,
      Fässler & Meissner 2011). A person's expectation is an important part of the so-called
      placebo effect . The placebo effect is well known and clinically important phenomenon in the
      patient's treatment. Extensive research has been conducted to elucidate this (Meissner et al
      2011; Collocca et al 2013; Enck et al 2013).

      Patients with substance syndrome often have other expectations for the drug compared to
      patients with other diagnoses. Some of these patients have often learned to deal with awkward
      and difficult life situations using drugs (Whalen & Henker 1976; Pelham & Lang 1993). This
      may increases the risk that the person receives a low confidence in their own ability to
      solve critical situations without drugs. Therefore, it is important to identify those
      patients in order to give them a treatment specialized to their need.

      This study intends to investigate whether the patient's expectation of their own ability to
      solve problems increases when they take a drug.

      Aim: The purpose of the study is to examine the effects of medication, placebo and
      expectation on objective and self-rated performance of ADHD core signs during the Quantified
      Behavior Test in patients with untreated ADHD and substance Use Disorders.

      This leads to the following questions ;

        1. Does the participant's self-rated expectation of future performance change in the
           presence of active drug or placebo?

        2. Does the participant's self-rated performance change in the presence of active drug or
           placebo?

        3. Does the participant's perception of exertion change in the presence of active drug or
           placebo?

        4. Does the participant's performance on the core signs, Hyperactivity, Inattention and
           Impulsivity on the QbTest change in the presence of active drug or placebo ?

        5. Does the participant's experience of the tablet's efficacy change in the presence of
           active drug or placebo?

      Method: The study is a double-blind, randomized, placebo-controlled, cross-over study. The
      study is taken place during four hours on two investigating days, separated by a 4 days
      wash-out period.

      Subjects: Participants are 40 consecutive patients remitted to a neuropsychiatric
      investigation at the Dependence Clinic Västmanland, Västerås, Sweden.

      Instruments The Quantized Behavior Test (QbTest) can be included as part of an
      neuropsychiatric investigation. QbTest measures the three core signs of ADHD, hyperactivity,
      inattention and impulsivity.

      The QbTest combines a Continuous Performance Test (CPT) installed as a software program on a
      computer with measures of attention and impulsivity and an activity test with measures of
      motor-activity during 20 minutes. While performing the CPT-test on the computer, movements of
      the participant are recorded using an infrared camera following a reflective marker attached
      to a head-band. The CPT-test involves rapid presentations of figures with various shapes
      (square or circle) and colors (red or blue) and the participant are instructed to press a
      handheld button when a stimuli subsequently repeats itself (a target) and not to press the
      button when the stimulus varies relative to the previous one (a non-target). The stimuli are
      presented at a pace of one per two seconds, each one visible for 200 milliseconds, and the
      total number of stimuli is 600, presented with a 25% target probability (Knagenhjelm &
      Ulberstad 2010).

      The clinical documentation for QbTest is extensive. Lis et al demonstrated that patients with
      ADHD were significantly different in the variables of attention and activity from a control
      group of healthy individuals (Lis et al 2010). Edebol showed that QbTest has a sensitivity of
      83 % and a specificity of 57% to detect ADHD in adults (Edebol et al 2011).

      The discriminative validity was tested and the results show that QbTest differ not only
      between those with ADHD and healthy controls , but between clients with ADHD and other
      clinical groups (Söderström, Pettersson & Nilsson 2014; Edebol, Helldin & Norlander 2012).
      QbTest has also shown good results as an objective method for monitoring drug treatment with
      methylphenidate (Ginsberg, Hirvikoski & Grann 2012; Edebol, Helldin & Norlander 2013;
      Bijlenga & Henker 2014).

      The Quick Test measure processing speed and automaticity of naming shapes and colours,
      Cognitive shifts between visual dimensions and semantic fields and Activation of working
      memory for processing and monitoring. AQT's objective measures are based on clocked
      total-naming time. Highly reliable (r = .88 - 96) over time and consistent over repeated
      trials.

      Procedure:

      All patients participate on two occasions: In one session they receive the Methylphenidate
      (MPH) condition, and in the other session they receive the placebo condition. MPH and placebo
      conditions are counterbalanced across subjects such that half of the participants receive MPH
      first, and the other half of the participants receive placebo first. Neither the participant
      nor the research assistant is aware when the participant receive the MPH condition or the
      placebo condition.

      On each investigating day the participant accomplish Questionnaires (Visual Analogical
      Scales) concerning; (a) expectation, (b) self-rated performance, (c) exhausting exercise, (d)
      perceived help from the pill and (e) self-rated symptoms. In addition the participant
      completed A Quick Test of Cognitive Speed (AQT) and two separate Quantified Behavior Test
      Plus (QbTest) without medication vs MPH/Placebo.

      Analyses In this study, hyperactivity has been operationalized with the parameter called
      "distance", i.e., the length of the path in metres describing the movement of the headband
      reflector during the test period. Inattention is operationalized on the basis of omission
      errors. An omission error occurs when no response is registered when the stimulus was a
      Target, i.e. the button was not pressed when it should have been. Impulsivity is
      operationalized on the bases of commission errors. A commission error occurs when a response
      is registered when the stimulus was a Non-Target, i.e. the handheld button is pressed when it
      should not have been pressed.
    

Intervention name(s): Methylphenidate; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Cross-over; Medikinet
Other intervention name(s): Medikinet; Medikinet
Intervention MeSH terms: Methylphenidate
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Basic Science