Effects of Expectation, Medication and Placebo on Objective and Self-rated Performance During the QbTest
Condition: Attention Deficit Hyperactivity Disorder
MeSH terms: 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.

      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 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. 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.

      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. QbTest is a computer-based test that combines a test of attention ability with a
      movement analysis based on an infrared measurement system. The test results are presented in
      a report and compared with norm data fromm a group of the same sex amd age who do not have
      ADHD.
    

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