The indication of attention-deficit/hyperactivity disorder (ADHD) to be examined often occurs with other psychiatric disorders, and the majority of adults with ADHD have at least one psychiatric comorbidity in their lives. Depression is one of the most common comorbidities in patients with ADHD. The prevalence of comorbid depression in adults with ADHD is estimated to be as high as 50%. There is evidence that stimulants such as dexamfetamine and methylphenidate lead to an improvement in sustained focused attention, working memory, and a variety of cognitive processes in the prefrontal cortex (PFC). In combination with the pharmacological effects of stimulants, such as the inhibition of monoamine oxidase, the increase in the concentration of noradrenaline in the PFC and dopamine in the striatum, dexamfetamine and methylphenidate could improve the treatment of depression in patients with major depressive disorder and comorbid ADHD. This clinical trial will evaluate the safety and efficacy of DEX in two different formulations compared to placebo in adults with ADHD and moderate to severe depression. To ensure double blinding of the treatment, placebo will be administered in the form of tablets and capsules.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
105
tablet twice daily
capsule once daily
Placebo to either capsule or tablet
Department of Psychiatry, Psychosomatics and Psychotherapy University Hospital Frankfurt am Main - Goethe University
Frankfurt, Germany
RECRUITINGUniversity Leipzig, Department of Psychiatry and Psychotherapy
Leipzig, Germany
RECRUITINGIncidence of adverse events (AE) in the active treatment groups compared to the placebo until V6
Incidence of adverse events (AE) in the active treatment groups (DEX XL and DEX IR) compared to the placebo until V6
Time frame: from enrollment to the end of study at week 17
Incidence of adverse events (AE) until V5
Dokumentation of AE
Time frame: Start with enrollment until end of treatment at Week 16
Proportion of patients with at least one AE until V5
Proportion of patients with at least one AE until V5
Time frame: through study treatment (up to 16 weeks)
Proportion of patients with at least one AE until end of study
Proportion of patients with at least one AE until end of study
Time frame: from baseline until end of study at week 17
Number of AE until V5
Number of AE
Time frame: through study treatment (up to 16 weeks)
Number of AE until V5 and until end of study
Number of AE
Time frame: from baseline until end of study at week 17
Number of AE/SAE during the study period
Number of AE/SAE
Time frame: through study treatment (up to 16 weeks)
number of patients with AE/SAE by type during study period
Number and type of AE/SAE
Time frame: through study treatment (up to 16 weeks)
proportion of patients with AE/SAE by type during study period
Proportion of patient with AE/SAE by type
Time frame: through study treatment (up to 16 weeks)
number of patients with AE/SAE by severity (mild, moderate, severe) during study period
number of patients with AE/SAE by severity (mild, moderate, severe)
Time frame: through study treatment (up to 16 weeks)
proportion of patients with AE/SAE by severity (mild, moderate, severe) during study period
proportion of patients with AE/SAE by severity (mild, moderate, severe)
Time frame: through study treatment (up to 16 weeks)
number of patients with AE/SAE by relatedness to treatment during study period
number of patients with AE/SAE by relatedness to treament
Time frame: through study treatment (up to 16 weeks)
proportion of patients with AE/SAE by relatedness to treatment during study period
proportion of patients with AE/SAE by relatedness to treatment
Time frame: from enrollment to the end of study at week 17
Score of clinical global impression (CGI) Efficacy index by investigator at Visit 5
Clinical global impression (CGI) rating scales are measures of symptom severity, treatment response and the efficacy of treatments in patients with mental disorders. It is a brief 3-item observer-rated scale. 4×4 rating scale that assesses the therapeutic effect of treatment with psychiatric medication and associated side effects. Treatment is evaluated from "marked improvement" to "none/worsening". Side effects is evaluated from "none" to "outweigh therapeutic effect"
Time frame: 16 weeks after treatment start
MADRS suicidal ideation score for all available visits (screening to Visit 5)
Montgomery-Åsberg Depression Rating Scale (MADRS) is a ten-item diagnostic questionnaire used to measure the severity of depressive episodes in patients with mood disorders. The questionnaire includes questions on ten symptoms related to depression. Each item yields a score of 0 to 6; the overall score thus ranges from 0 to 60. Higher MADRS score indicates more severe depression.
Time frame: from enrollment to the end of treatment (up to week 16)
MADRS suicidal ideation score for all available visits
Montgomery-Åsberg Depression Rating Scale (MADRS) is a ten-item diagnostic questionnaire used to measure the severity of depressive episodes in patients with mood disorders. The questionnaire includes questions on ten symptoms related to depression. Each item yields a score of 0 to 6; the overall score thus ranges from 0 to 60. Higher MADRS score indicates more severe depression.
Time frame: from enrollment to end of titration at week 4 (V1)
MADRS suicidal ideation score for all available visits
Montgomery-Åsberg Depression Rating Scale (MADRS) is a ten-item diagnostic questionnaire used to measure the severity of depressive episodes in patients with mood disorders. The questionnaire includes questions on ten symptoms related to depression. Each item yields a score of 0 to 6; the overall score thus ranges from 0 to 60. Higher MADRS score indicates more severe depression.
Time frame: from enrollment to week 7 (V2)
MADRS suicidal ideation score change to BL/V0 (on V1)
Montgomery-Åsberg Depression Rating Scale (MADRS) is a ten-item diagnostic questionnaire used to measure the severity of depressive episodes in patients with mood disorders. The questionnaire includes questions on ten symptoms related to depression. Each item yields a score of 0 to 6; the overall score thus ranges from 0 to 60. Higher MADRS score indicates more severe depression.
Time frame: from baseline to end of treatment titration phase at 4 weeks
MADRS suicidal ideation score change to BL/V0 (on V5)
Montgomery-Åsberg Depression Rating Scale (MADRS) is a ten-item diagnostic questionnaire used to measure the severity of depressive episodes in patients with mood disorders. The questionnaire includes questions on ten symptoms related to depression. Each item yields a score of 0 to 6; the overall score thus ranges from 0 to 60. Higher MADRS score indicates more severe depression.
Time frame: from treatment start to end of treatment at 16 weeks
MADRS suicidal ideation score for all available visits
Montgomery-Åsberg Depression Rating Scale (MADRS) is a ten-item diagnostic questionnaire used to measure the severity of depressive episodes in patients with mood disorders. The questionnaire includes questions on ten symptoms related to depression. Each item yields a score of 0 to 6; the overall score thus ranges from 0 to 60. Higher MADRS score indicates more severe depression.
Time frame: from enrollment to 10 weeks (V3)
MADRS suicidal ideation score for all available visits
Montgomery-Åsberg Depression Rating Scale (MADRS) is a ten-item diagnostic questionnaire used to measure the severity of depressive episodes in patients with mood disorders. The questionnaire includes questions on ten symptoms related to depression. Each item yields a score of 0 to 6; the overall score thus ranges from 0 to 60. Higher MADRS score indicates more severe depression.
Time frame: from enrollment to 13 weeks (V4)
MADRS suicidal ideation score for all available visits (screening to visit 5)
Montgomery-Åsberg Depression Rating Scale (MADRS) is a ten-item diagnostic questionnaire used to measure the severity of depressive episodes in patients with mood disorders. The questionnaire includes questions on ten symptoms related to depression. Each item yields a score of 0 to 6; the overall score thus ranges from 0 to 60. Higher MADRS score indicates more severe depression.
Time frame: from enrollment to 16 weeks (V5)
Rate of patients with score 1-3 in CGI-I at V5
The clinical global impression - improvement scale (CGI-I) is a 7-point scale that requires the clinician to assess how much the patient's illness has improved or worsened relative to a baseline state at the beginning of the intervention. Clinicians ask: "Compared to the patient's condition at baseline, this patient's \[average\] condition has...?" and rated as: Very much improved Much improved Minimally improved No change Minimally worse Much worse Very much worse
Time frame: from baseline to 16 weeks (V5)
Absolute scores categories of CGI-I at all available visits
The clinical global impression - improvement scale (CGI-I) is a 7-point scale that requires the clinician to assess how much the patient's illness has improved or worsened relative to a baseline state at the beginning of the intervention. Clinicians ask: "Compared to the patient's condition at baseline, this patient's \[average\] condition has...?" and rated as: Very much improved Much improved Minimally improved No change Minimally worse Much worse Very much worse
Time frame: from end of treatment titration phase at 4 weeks (V1) to week 7 (V2)
Absolute scores categories of CGI-I at all available visits (V1 to V2)
The clinical global impression - improvement scale (CGI-I) is a 7-point scale that requires the clinician to assess how much the patient's illness has improved or worsened relative to a baseline state at the beginning of the intervention. Clinicians ask: "Compared to the patient's condition at baseline, this patient's \[average\] condition has...?" and rated as: Very much improved Much improved Minimally improved No change Minimally worse Much worse Very much worse
Time frame: from end of titration phase (week 4) to 7 weeks (V2)
Absolute scores categories of CGI-I at all available visits (V1 to V3)
The clinical global impression - improvement scale (CGI-I) is a 7-point scale that requires the clinician to assess how much the patient's illness has improved or worsened relative to a baseline state at the beginning of the intervention. Clinicians ask: "Compared to the patient's condition at baseline, this patient's \[average\] condition has...?" and rated as: Very much improved Much improved Minimally improved No change Minimally worse Much worse Very much worse
Time frame: from end of titration phase (week 4) to 10 weeks (V3)
Absolute scores categories of CGI-I at all available visits (V1 to V4)
The clinical global impression - improvement scale (CGI-I) is a 7-point scale that requires the clinician to assess how much the patient's illness has improved or worsened relative to a baseline state at the beginning of the intervention. Clinicians ask: "Compared to the patient's condition at baseline, this patient's \[average\] condition has...?" and rated as: Very much improved Much improved Minimally improved No change Minimally worse Much worse Very much worse
Time frame: from end of titration phase (week 4) to 13 weeks (V4)
Absolute scores categories of CGI-I at all available visits (V1 to V5)
The clinical global impression - improvement scale (CGI-I) is a 7-point scale that requires the clinician to assess how much the patient's illness has improved or worsened relative to a baseline state at the beginning of the intervention. Clinicians ask: "Compared to the patient's condition at baseline, this patient's \[average\] condition has...?" and rated as: Very much improved Much improved Minimally improved No change Minimally worse Much worse Very much worse
Time frame: from end of titration phase (week 4) to end of treatment at 16 weeks (V5)
Numbers and percentages of patients with (1) decreased, (2) maintained and (3) increased CGI-S at V5 compared to BL/V0
The clinical global impression - severity scale (CGI-S) is a 7-point scale that requires the clinician to rate the severity of the patient's illness at the time of assessment, relative to the clinician's past experience with patients who have the same diagnosis. Clinicians ask: "Considering your total clinical experience with this particular population, how ill is the patient at this time?" Possible ratings are: Normal, not at all ill Borderline mentally ill Mildly ill Moderately ill Markedly ill Severely ill Among the most extremely ill patients
Time frame: from baseline to end of treatment at 16 weeks (V5)
Shift table of CGI-S score categories at BL/V0
The clinical global impression - severity scale (CGI-S) is a 7-point scale that requires the clinician to rate the severity of the patient's illness at the time of assessment, relative to the clinician's past experience with patients who have the same diagnosis. Clinicians ask: "Considering your total clinical experience with this particular population, how ill is the patient at this time?" Possible ratings are: Normal, not at all ill Borderline mentally ill Mildly ill Moderately ill Markedly ill Severely ill Among the most extremely ill patients
Time frame: at baseline
Shift table of CGI-S score categories at V1
The clinical global impression - severity scale (CGI-S) is a 7-point scale that requires the clinician to rate the severity of the patient's illness at the time of assessment, relative to the clinician's past experience with patients who have the same diagnosis. Clinicians ask: "Considering your total clinical experience with this particular population, how ill is the patient at this time?" Possible ratings are: Normal, not at all ill Borderline mentally ill Mildly ill Moderately ill Markedly ill Severely ill Among the most extremely ill patients
Time frame: from baseline to end of treatment titration phase at 4 weeks (V1)
Shift table of CGI-S score categories at V5
The clinical global impression - severity scale (CGI-S) is a 7-point scale that requires the clinician to rate the severity of the patient's illness at the time of assessment, relative to the clinician's past experience with patients who have the same diagnosis. Clinicians ask: "Considering your total clinical experience with this particular population, how ill is the patient at this time?" Possible ratings are: Normal, not at all ill Borderline mentally ill Mildly ill Moderately ill Markedly ill Severely ill Among the most extremely ill patients
Time frame: from baseline to end of treatment at 16 weeks (V5)
Absolute score categories of CGI-S at V0
The clinical global impression - severity scale (CGI-S) is a 7-point scale that requires the clinician to rate the severity of the patient's illness at the time of assessment, relative to the clinician's past experience with patients who have the same diagnosis. Clinicians ask: "Considering your total clinical experience with this particular population, how ill is the patient at this time?" Possible ratings are: Normal, not at all ill Borderline mentally ill Mildly ill Moderately ill Markedly ill Severely ill Among the most extremely ill patients
Time frame: at baseline (V0)
Absolute score categories of CGI-S at V0 to V2
The clinical global impression - severity scale (CGI-S) is a 7-point scale that requires the clinician to rate the severity of the patient's illness at the time of assessment, relative to the clinician's past experience with patients who have the same diagnosis. Clinicians ask: "Considering your total clinical experience with this particular population, how ill is the patient at this time?" Possible ratings are: Normal, not at all ill Borderline mentally ill Mildly ill Moderately ill Markedly ill Severely ill Among the most extremely ill patients
Time frame: from baseline to 7 weeks (V2)
Absolute score categories of CGI-S at V0 to V1
The clinical global impression - severity scale (CGI-S) is a 7-point scale that requires the clinician to rate the severity of the patient's illness at the time of assessment, relative to the clinician's past experience with patients who have the same diagnosis. Clinicians ask: "Considering your total clinical experience with this particular population, how ill is the patient at this time?" Possible ratings are: Normal, not at all ill Borderline mentally ill Mildly ill Moderately ill Markedly ill Severely ill Among the most extremely ill patients
Time frame: from baseline to end of treatment titration phase at 4 weeks (V1)
Absolute score categories of CGI-S at V0 to V3
The clinical global impression - severity scale (CGI-S) is a 7-point scale that requires the clinician to rate the severity of the patient's illness at the time of assessment, relative to the clinician's past experience with patients who have the same diagnosis. Clinicians ask: "Considering your total clinical experience with this particular population, how ill is the patient at this time?" Possible ratings are: Normal, not at all ill Borderline mentally ill Mildly ill Moderately ill Markedly ill Severely ill Among the most extremely ill patients
Time frame: from baseline to 10 weeks (V3)
Absolute score categories of CGI-S at V0 to V4
The clinical global impression - severity scale (CGI-S) is a 7-point scale that requires the clinician to rate the severity of the patient's illness at the time of assessment, relative to the clinician's past experience with patients who have the same diagnosis. Clinicians ask: "Considering your total clinical experience with this particular population, how ill is the patient at this time?" Possible ratings are: Normal, not at all ill Borderline mentally ill Mildly ill Moderately ill Markedly ill Severely ill Among the most extremely ill patients
Time frame: from baseline to 13 weeks (V4)
Absolute score categories of CGI-S at V0 to V5
The clinical global impression - severity scale (CGI-S) is a 7-point scale that requires the clinician to rate the severity of the patient's illness at the time of assessment, relative to the clinician's past experience with patients who have the same diagnosis. Clinicians ask: "Considering your total clinical experience with this particular population, how ill is the patient at this time?" Possible ratings are: Normal, not at all ill Borderline mentally ill Mildly ill Moderately ill Markedly ill Severely ill Among the most extremely ill patients
Time frame: from baseline to end of treatment at 16 weeks (V5)
MADRS total score (range 0-60) for all available visits (SCR to V5)
Montgomery-Åsberg Depression Rating Scale (MADRS) is a ten-item diagnostic questionnaire used to measure the severity of depressive episodes in patients with mood disorders. The questionnaire includes questions on ten symptoms related to depression. Each item yields a score of 0 to 6; the overall score thus ranges from 0 to 60. Higher MADRS score indicates more severe depression.
Time frame: Screening until end of treatment at week 16 (V5)
MADRS total score (range 0-60) MADRS total score (range 0-60) change to BL/V0 (at V5)
Montgomery-Åsberg Depression Rating Scale (MADRS) is a ten-item diagnostic questionnaire used to measure the severity of depressive episodes in patients with mood disorders. The questionnaire includes questions on ten symptoms related to depression. Each item yields a score of 0 to 6; the overall score thus ranges from 0 to 60. Higher MADRS score indicates more severe depression.
Time frame: baseline until end of treatment at week 16 (V5)
MADRS total score categorization by Müller et al. at BL/ V0
MADRS total score categorization by Müller et al.: 0-6 absence of symptoms; 7-19 mild depression, 20-34 moderate depression, 35-60 indicate a severe depression.
Time frame: at baseline
ADHS-DC-Q total score (range 0-66) for all available visits (SCR to V5)
The ADHS-DC-Q consists of 18 items with a four-level response (not existing, slightly existing, moderately existing, strongly existing). The items ask about the current symptoms. The three scales are: lack of inattentiveness, hyperactivity and impulsiveness.
Time frame: Screening to end of treatment at week 16
ADHS-DC-Q total score (range 0-66) change to BL/V0 (V1)
The ADHS-DC-Q consists of 18 items with a four-level response (not existing, slightly existing, moderately existing, strongly existing). The items ask about the current symptoms. The three scales are: lack of inattentiveness, hyperactivity and impulsiveness.
Time frame: from baseline to end of titration at week 4 (V1)
QIDS-SR-16 total score (range 0-27) for all available visits (V0 to V5)
QIDS-SR-16 is a self-report measure of depression consisting of 16 items. Questions in the QIDS - SR-16 correlate with the nine DSM-IV symptom criterion domains, Including: Sleep disturbance (initial, middle, and late insomnia or hypersomnia), Sad mood, Decrease/increase in appetite/weight , Concentration , Self-criticism, Suicidal ideation, Interest, Energy/fatigue, Psychomotor agitation/retardation. Scoring is given from 0 to 3 whereas 0 indicates less impact, 3 highest impact in depression.
Time frame: baseline to end of treatment at 16 weeks
QIDS-SR-16 total score (range 0-27) change to BL/V0 (V5)
QIDS-SR-16 is a self-report measure of depression consisting of 16 items. Questions in the QIDS - SR-16 correlate with the nine DSM-IV symptom criterion domains, Including: Sleep disturbance (initial, middle, and late insomnia or hypersomnia), Sad mood, Decrease/increase in appetite/weight , Concentration , Self-criticism, Suicidal ideation, Interest, Energy/fatigue, Psychomotor agitation/retardation. Scoring is given from 0 to 3 whereas 0 indicates less impact, 3 highest impact in depression.
Time frame: from baseline to end of treatment at week 16 (V5)
Mean dose intake from V1 to V5 per treatment group
Mean dose intake from V1 to V5 per treatment group
Time frame: from end of titration (week 4, V1) until end of treatment at week 16
Mean dose intake compared to planned dose after titration phase (for study period V1 to V5) per treatment group
Mean dose intake compared to planned dose after titration phase per treatment group
Time frame: end of titration phase (visit 1) 4 weeks after baseline until end of treatment at week 16 (12 weeks after titration phase)
Proportion of patients with less than 80% of planned dose intake (for study period V1 to V5) per treatment group
Proportion of patients with less than 80% of planned dose intake per treatment group
Time frame: visit 1 (4 weeks after baseline) until end of treatment at week 16
Number of patients by dosage group at V1 and V2
Number of patients by dosage group (DEX IR: 10 mg, 15 mg, 20 mg, 30 mg; DEX XL: 10 mg, 15 mg, 20 mg, 30 mg; Placebo: 10 mg, 15 mg, 20 mg, 30 mg))
Time frame: at visit 1 (4 weeks after baseline) and at visit 2 (3 weeks after visit 1)
Proportion of patients by dosage group at V1 and V2
Proportion of patients by dosage group (DEX IR: 10 mg, 15 mg, 20 mg, 30 mg; DEX XL: 10 mg, 15 mg, 20 mg, 30 mg; Placebo: 10 mg, 15 mg, 20 mg, 30 mg))
Time frame: at visit 1 (4 weeks after baseline) and at visit 2 (3 weeks after visit 1)
Number of patients per treatment group that needed dose optimization of IMP in the optimal stable dose phase and type of optimization (e.g., downtitration)
Number of patients per treatment group that needed dose optimization of IMP in the optimal stable dose phase and type of optimization (e.g., downtitration)
Time frame: end of titration phase (visit 1) 4 weeks after baseline until end of treatment at week 16 (12 weeks after titration phase)
Proportion of patients per treatment group that needed dose optimization of IMP in the optimal stable dose phase and type of optimization (e.g., downtitration)
Proportion of patients per treatment group that needed dose optimization of IMP in the optimal stable dose phase and type of optimization (e.g., downtitration)
Time frame: end of titration phase (visit 1) 4 weeks after baseline until end of treatment at week 16 (12 weeks after titration phase)
Number of patients with early withdrawal from therapy due to adverse events
Number of patients with early withdrawal from therapy due to adverse events in total
Time frame: baseline until end of treatment at week 16 (12 weeks after end of titration phase)
Number of patients with early withdrawal from therapy due to adverse events per treatment group
Number of patients with early withdrawal from therapy due to adverse events per treatment group
Time frame: baseline until end of treatment at week 16 (12 weeks after end of titration phase)
percentage of patients with early withdrawal from therapy due to adverse events in total
Percentage of patients with early withdrawal from therapy due to adverse events - in total
Time frame: baseline until end of treatment at week 16 (12 weeks after end of titration phase)
Percentage of patients with early withdrawal from therapy due to adverse events per treatment group
Percentage of patients with early withdrawal from therapy due to adverse events per treatment group
Time frame: baseline until end of treatment at week 16 (12 weeks after end of titration phase)
MADRS total score categorization by Müller et al. at BL/ V0, V1 and V5
MADRS total score categorization by Müller et al.: 0-6 absence of symptoms; 7-19 mild depression, 20-34 moderate depression, 35-60 indicate a severe depression.
Time frame: at baseline, at end of titration phase (week 4) and at end of treatment (week 16, V5)
MADRS total score (range 0-60) MADRS total score (range 0-60) change to BL/V0 (at V1)
Montgomery-Åsberg Depression Rating Scale (MADRS) is a ten-item diagnostic questionnaire used to measure the severity of depressive episodes in patients with mood disorders. The questionnaire includes questions on ten symptoms related to depression. Each item yields a score of 0 to 6; the overall score thus ranges from 0 to 60. Higher MADRS score indicates more severe depression.
Time frame: baseline until end of titration phase at week 4 (V1)
ADHS-DC-Q total score (range 0-66) change to BL/V0 (V1)
The ADHS-DC-Q consists of 18 items with a four-level response (not existing, slightly existing, moderately existing, strongly existing). The items ask about the current symptoms. The three scales are: lack of inattentiveness, hyperactivity and impulsiveness.
Time frame: baseline until end of titration phase at week 4 (V1)
ADHS-DC-Q total score (range 0-66) change to BL/V0 (to V5)
The ADHS-DC-Q consists of 18 items with a four-level response (not existing, slightly existing, moderately existing, strongly existing). The items ask about the current symptoms. The three scales are: lack of inattentiveness, hyperactivity and impulsiveness.
Time frame: baseline until end of treatment at week 16 (V5)
QIDS-SR-16 total score (range 0-27) change to BL/V0 (V1)
QIDS-SR-16 is a self-report measure of depression consisting of 16 items. Questions in the QIDS - SR-16 correlate with the nine DSM-IV symptom criterion domains, Including: Sleep disturbance (initial, middle, and late insomnia or hypersomnia), Sad mood, Decrease/increase in appetite/weight , Concentration , Self-criticism, Suicidal ideation, Interest, Energy/fatigue, Psychomotor agitation/retardation. Scoring is given from 0 to 3 whereas 0 indicates less impact, 3 highest impact in depression.
Time frame: from baseline to end of titration (week 4, V1)
MADRS suicidal ideation score for all available visits
Montgomery-Åsberg Depression Rating Scale (MADRS) is a ten-item diagnostic questionnaire used to measure the severity of depressive episodes in patients with mood disorders. The questionnaire includes questions on ten symptoms related to depression. Each item yields a score of 0 to 6; the overall score thus ranges from 0 to 60. Higher MADRS score indicates more severe depression.
Time frame: from enrollment to baseline (start of treatment, V0)
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