Challenges of Treating ADHD with Comorbid Substance Use Disorder: Considerations for the Clinician.

Adults with attention deficit/hyperactivity disorder (ADHD) often present psychiatric comorbidities and, in particular, substance use disorder (SUD). ADHD-SUD comorbidity is characterized by greater severity of both disorders, earlier age of onset, higher likelihood of polydrug-abuse and suicidal behaviors, more hospitalizations, and lower treatment adherence. At the present stage, research focused on the pharmacological management of ADHD with comorbid SUD in both adolescents and adults is still lacking. Furthermore, while the short-term effects of stimulants are well studied, less is known about the chronic effects of these drugs on dopamine signaling. Current available evidence is consistent in reporting that high doses of stimulant medications in ADHD-SUD subjects have a mild to moderate efficacy on ADHD symptoms. Some data suggest that pharmacological treatment with stimulants may be beneficial for both ADHD symptoms and comorbid cocaine or amphetamine use. However, in the long run, stimulant medications may have a potential risk for misuse. For the absence of potential misuse, atomoxetine is often recommended for ADHD with comorbid cocaine or amphetamine use disorder. However, its efficacy in reducing addictive behavior is not demonstrated. In subjects with other subtypes of SUD, both atomoxetine and stimulant drugs seem to have scarce impact on addictive behavior, despite the improvement in ADHD symptomatology. In this population, ADHD treatment should be combined with SUD-specific strategies.

Adult Attention-Deficit Hyperactivity Disorder/Substance Use Disorder Dual Disorder Patients: A Dual Disorder Unit Point of View.

Substance Use Disorders (SUDs) are often associated with Attention-Deficit Hyperactivity Disorder (ADHD) in adult populations due to multiple neurobiological, genetic, and psychosocial risk factors. This chapter provides a picture of the clinical aspects of adults with both ADHD and SUDs at treatment entry into a Dual Disorder Unit introducing the concept of different types of craving that may lead to substance use and abuse. At treatment entry, the presence of different comorbid SUD clusters, characterized by either stimulants/alcohol or by the use of cannabinoids, has not been shown to influence ADHD-specific symptomatology or severity, despite being crucial for the identification of a specific type of craving. We identified four clinical presentations of adult ADHD: Emotional Dysregulation, Substance Use, Core-ADHD Symptoms, and Positive Emotionality variants, that offer a practical guide in diagnosing and managing adult ADHD patients. Although the evidence of an effective medical treatment for Cocaine Use Disorder is insufficient, in our experience, toxicomanic behavior during stimulant treatment is sharply reduced in ADHD patients with cocaine addiction. Moreover, caffeinated compounds in military soldiers with ADHD may help reduce ADHD symptoms, making caffeine a potential pharmacological tool worth further investigation. Finally, substance use comorbidity does not influence treatment retention rate.

Pilot Study on Dose-Dependent Effects of Transcranial Photobiomodulation on Brain Electrical Oscillations: A Potential Therapeutic Target in Alzheimer's Disease.

BACKGROUND: Transcranial photobiomodulation (tPBM) has recently emerged as a potential cognitive enhancement technique and clinical treatment for various neuropsychiatric and neurodegenerative disorders by delivering invisible near-infrared light to the scalp and increasing energy metabolism in the brain. OBJECTIVE: We assessed whether transcranial photobiomodulation with near-infrared light modulates cerebral electrical activity through electroencephalogram (EEG) and cerebral blood flow (CBF). METHODS: We conducted a single-blind, sham-controlled pilot study to test the effect of continuous (c-tPBM), pulse (p-tPBM), and sham (s-tPBM) transcranial photobiomodulation on EEG oscillations and CBF using diffuse correlation spectroscopy (DCS) in a sample of ten healthy subjects [6F/4 M; mean age 28.6±12.9 years]. c-tPBM near-infrared radiation (NIR) (830 nm; 54.8 mW/cm2; 65.8 J/cm2; 2.3 kJ) and p-tPBM (830 nm; 10 Hz; 54.8 mW/cm2; 33%; 21.7 J/cm2; 0.8 kJ) were delivered concurrently to the frontal areas by four LED clusters. EEG and DCS recordings were performed weekly before, during, and after each tPBM session. RESULTS: c-tPBM significantly boosted gamma (t = 3.02, df = 7, p < 0.02) and beta (t = 2.91, df = 7, p < 0.03) EEG spectral powers in eyes-open recordings and gamma power (t = 3.61, df = 6, p < 0.015) in eyes-closed recordings, with a widespread increase over frontal-central scalp regions. There was no significant effect of tPBM on CBF compared to sham. CONCLUSION: Our data suggest a dose-dependent effect of tPBM with NIR on cerebral gamma and beta neuronal activity. Altogether, our findings support the neuromodulatory effect of transcranial NIR.

Does Cannabis, Cocaine and Alcohol Use Impact Differently on Adult Attention Deficit/Hyperactivity Disorder Clinical Picture?

While the association between adult Attention Deficit/Hyperactivity Disorder (A-ADHD) and Substance Use Disorders (SUDs) has been widely explored, less attention has been dedicated to the various substance use variants. In a previous paper, we identified two variants: type 1 (use of stimulants/alcohol) and type 2 (use of cannabinoids). In this study, we compared demographic, clinical and symptomatologic features between Dual Disorder A-ADHD (DD/A-ADHD) patients according to our substance use typology, and A-ADHD without DD (NDD/A-ADHD) ones. NDD patients were more frequently diagnosed as belonging to inattentive ADHD subtype compared with type 1 DD/A-ADHD patients, but not with respect to type 2 DD/ADHD. NDD/A-ADHD patients showed less severe symptoms of hyperactivity/impulsivity than DD/A-ADHD type 1, but not type 2. Type 1 and type 2 patients shared the feature of displaying higher impulsiveness than NDD/A-ADHD ones. General psychopathology scores were more severe in type 2 DD/ADHD patients, whereas type 1 patients showed greater similarity to NDD/A-ADHD. Legal problems were more strongly represented in type 1 than in type 2 patients or NDD/A-ADHD ones. Our results suggest that type 1 and type 2 substance use differ in their effects on A-ADHD patients-an outcome that brings with it different likely implications in dealing with the diagnostic and therapeutic processes.

Assessing the Magnitude of Risk for ADHD in Offspring of Parents with ADHD: A Systematic Literature Review and Meta-Analysis.

The main aim of this study was to examine the body of knowledge on the prevalence of Attention Deficit Hyperactivity Disorder (ADHD) in "high-risk" children whose parents are diagnosed with ADHD. This knowledge could aid early identification for children presenting with ADHD symptoms at a young age. We conducted a systematic search of the literature assessing high-risk children. Included were original articles published in English with the main aim to assess prevalence of ADHD in high risk children. In addition, a meta-analysis was conducted to examine this prevalence. Four articles met our inclusion and exclusion criteria all suggesting an increased prevalence of ADHD in children of parents with ADHD. The meta-analysis also confirmed the increased prevalence of ADHD in high-risk children. The literature indicates that children of ADHD parents have an increased risk of developing ADHD compared to control children.

Differentiating bipolar disorder from unipolar depression in youth: A systematic literature review of neuroimaging research studies.

Differentiating bipolar disorder from unipolar depression is one of the most difficult clinical questions posed in pediatric psychiatric practices, as misdiagnosis can lead to severe repercussions for the affected child. This study aimed to examine the existing literature that investigates brain differences between bipolar and unipolar mood disorders in children directly, across all neuroimaging modalities. We performed a systematic literature search through PubMed, PsycINFO, Embase, and Medline databases with defined inclusion and exclusion criteria. Nine research studies were included in the systematic qualitative review, including three structural MRI studies, five functional MRI studies, and one MR spectroscopy study. Relevant variables were extracted and brain differences between bipolar and unipolar mood disorders in children as well as healthy controls were qualitatively analyzed. Across the nine studies, our review included 228 subjects diagnosed with bipolar disorder, 268 diagnosed with major depressive disorder, and 299 healthy controls. Six of the reviewed studies differentiated between bipolar and unipolar mood disorders. Differentiation was most commonly found in the anterior cingulate cortex (ACC), insula, and dorsal striatum (putamen and caudate) brain areas. Despite its importance, the current neuroimaging literature on this topic is scarce and presents minimal generalizability.

Adult attention-deficit hyperactivity disorder and clinical correlates of delayed sleep phase disorder.

The purpose of the study was to assess the prevalence and clinical correlates of Delayed Sleep Phase Disorder (DSPD) in adults with Attention-Deficit/Hyperactivity Disorder. Participants were 102 adults (Female= 27), aged 18-65 (mean age= 28.2 years), with ADHD diagnosed in adulthood. ADHD and DSPD diagnosis were made according to DSM-5 criteria. Assessing instruments included the Morningness-Eveningness Questionnaire, the brief Temperament Evaluation of Memphis, Pisa, Paris and San Diego Questionnaire, the Barratt Impulsiveness Scale, the Reactivity Intensity Polarity Stability Questionnaire-40 and the World Health Organization Disability Assessment Schedule 2.0. Epidemiological and Clinical features were compared in patients with and without DSPD. 34 out of 102 patients were classified as having a Delayed Sleep Phase Disorder. As expected, DSPD patients reported a more frequent evening chronotype. In the multivariate logistic regression analysis, Delayed Sleep Phase Disorder was significantly associated with young age, cannabis use, cyclothymic temperamental traits and severe global impairment. An early diagnosis with a proper treatment targeted to both disorders may be fundamental in order to improve the overall functioning and the outcome of adult ADHD patients.

Substance Use Disorder in Adult-Attention Deficit Hyperactive Disorder Patients: Patterns of Use and Related Clinical Features.

BACKGROUND: While a large amount of medical literature has explored the association between Attention Deficit/Hyperactivity Disorder (ADHD) and Substance Use Disorders (SUDs), less attention has been dedicated to the typologies of SUD and their relationships with ADHD-specific symptomatology and general psychopathology in dual disorder patients. METHODS: We selected 72 patients (aged 18-65) with a concomitant SUD out of 120 adults with ADHD (A-ADHD). Assessment instruments included the Diagnostic Interview for ADHD in adults (DIVA 2.0), Conner's Adult ADHD Rating Scales-Observer (CAARS-O:S): Short Version, the Structured Clinical Interview for Axis I and II Disorders (SCID-I), the Barratt Impulsiveness Scale (BIS-11), the Brief Psychiatric rating scale (BPRS), the Reactivity Intensity Polarity Stability Questionnaire (RIPoSt-40), the World Health Organization Disability Assessment Schedule (WHODAS 2.0) and the Morningness-Eveningness Questionnaire (MEQ). A factorial analysis was performed to group our patients by clusters in different typologies of substance use and correlations between SUDs, as made evident by their typological and diagnostic features; in addition, specific ADHD symptoms, severity of general psychopathology and patients' functionality were assessed. RESULTS: Two patterns of substance use were identified: the first (type 1) characterized by stimulants/alcohol and the second (type 2) by the use of cannabinoids (THC). Type 1 users were significantly younger and had more legal problems. The two patterns were similar in terms of ADHD-specific symptomatology and its severity at treatment entry. No differences were found regarding the other scales assessed, except for lower scores at MEQ in type 1 users. CONCLUSIONS: At treatment entry, the presence of different comorbid SUD clusters do not affect ADHD-specific symptomatology or severity.

Transcranial Photobiomodulation with Near-Infrared Light for Generalized Anxiety Disorder: A Pilot Study.

Objective: Our aim was to test the anxiolytic effect of transcranial photobiomodulation (t-PBM) with near-infrared light (NIR) in subjects suffering from generalized anxiety disorder (GAD). Background: t-PBM with NIR is an experimental, noninvasive treatment for mood and anxiety disorders. Preliminary evidence indicates a potential anxiolytic effect of transcranial NIR. Methods: Fifteen subjects suffering from GAD were recruited in an open-label 8-week study. Each participant self-administered t-PBM daily, for 20 min (continuous wave; 830 nm peak wavelength; average irradiance 30 mW/cm2; average fluence 36 J/cm2; total energy delivered per session 2.9 kJ: total output power 2.4 W) broadly on the forehead (total area 80 cm2) with an LED-cluster headband (Cerebral Sciences). Outcome measures were the reduction in total scores of the Hamilton Anxiety Scale (SIGH-A), the Clinical Global Impressions-Severity (CGI-S) subscale and the Pittsburgh Sleep Quality Index (PSQI) subscales from baseline to last observation carried forward. Results: Of the 15 recruited subjects (mean age 30 ± 14 years; 67% women), 12 (80%) completed the open trial. Results show a significant reduction in the total scores of SIGH-A (from 17.27 ± 4.89 to 8.47 ± 4.87; p < 0.001; Cohen's d effect size = 1.47), in the CGI-S subscale (from 4.53 ± 0.52 to 2.87 ± 0.83; p < 0.001; Cohen's d effect size = 2.04), as well as significant improvements in sleep at the PSQI. t-PBM was well tolerated with no serious adverse events. Conclusions: Based on our pilot study, t-PBM with NIR is a promising alternative treatment for GAD. Larger, randomized, double-blind, sham-controlled studies are needed.

The long-term outcome of patients with heroin use disorder/dual disorder (chronic psychosis) after admission to enhanced methadone maintenance.

BACKGROUND: Over-standard methadone doses are generally needed in the treatment of heroin use disorder (HUD) patients that display concomitant high-severity psychopathological symptomatology. A flexible dosing regimen may lead to higher retention rates in dual disorder (DD), as we demonstrated in bipolar 1 HUD patients, leading to outcomes that are as satisfactory as those of HUD patients without high-severity psychopathological symptomatology. OBJECTIVE: This study aimed to compare the long-term outcomes of treatment-resistant chronic psychosis HUD patients (PSY-HUD) with those of peers without dual disorder (HUD). METHODS: 85 HUD patients who also met the criteria for treatment resistance-25 of them affected by chronic psychosis and 60 without DD-were monitored prospectively for up to 8 years while continuing to receive enhanced methadone maintenance treatment. RESULTS: The rates of endurance in the treatment of PSY-HUD patients were 36%, compared with 34% for HUD patients (p = 0.872). After 3 years of treatment, these rates tended to become progressively more stable. PSY-HUD patients showed better outcome results than HUD patients regarding CGI severity (p < 0.001) and DSM-IV-GAF (p < 0.001). No differences were found regarding good toxicological outcomes or the methadone dosages used to achieve stabilization. The time required to stabilize PSY-HUD patients was shorter (p = 0.034). CONCLUSIONS: An enhanced methadone maintenance treatment seems to be equally effective in patients with PSY-HUD and those with HUD.

Further Evidence of a Specific Psychopathology of Addiction. Differentiation from Other Psychiatric Psychopathological Dimensions (Such as Obesity).

Introduction: In this study, we used a symptomatology checklist (SCL-90) to substantiate the hypothesis that Substance Use Disorder (SUD) has its own five-dimensional psychopathology. The aim of the present study was to test whether this psychopathology can be differentiated from other psychiatric psychopathological dimensions (such as obesity). Methods: The severity and frequency of each of the five dimensions were investigated, at univariate and multivariate levels, by comparing 972 Heroin Use Disorder (HUD) patients (83.5% male, mean age 30.12 ± 6.6, range: 16-59) and 106 obese individuals (50.0% male, mean age 37.59 ± 7.6, range: 24-52). The correlations between the Body Mass Index (BMI) of obese individuals with these psychopathological dimensions were also studied. Results: Obese individuals showed higher SCL-90 total scores, global severity index scores, number of items rated positively, and positive symptoms distress index scores than HUD patients. The severity of all psychopathological dimensions was significantly higher in obese individuals. Discriminant analysis showed that Panic-Anxiety and Violence-Suicide severity were more frequent in obese patients, sufficiently so to allow differentiation between HUD (lower severity) and obese individuals (greater severity). At the reclassification level, 70.8% of obese individuals in the sample were reclassified as HUD patients. Psychopathological subtypes characterized by Panic-Anxiety and Violence-Suicide typology were more frequent in obese patients and sufficiently so as to discriminate between groups. Of obese patients, 47.2% were reclassified as HUD patients. The severity of the Worthlessness-Being Trapped dimension was sufficient to predict the BMI of obese individuals. Conclusions: Our results suggest that the five-factor psychopathology found in HUD can discriminate between HUD and obese patients, but that there is an area of overlap between the forms of psychopathology found in SUD and those found in obese patients.

Opposed effects of hyperthymic and cyclothymic temperament in substance use disorder (heroin- or alcohol-dependent patients).

INTRODUCTION: In the last decade, the comprehension of affective temperaments has helped us to outline the boundaries of mood disorders, and to expand our knowledge of nosographic areas other than those of affectivity, even if affectivity is closely related to them. In the field of substance use disorders, the temperamental profile of heroin addicts and alcoholics has been discussed elsewhere, but no comparison has yet been made between these two patient populations. Such a comparison would help to shed light on the pathogenetic mechanisms that link temperament with substance abuse. METHODS: 63 Heroin Use Disorder (HUD) and 94 Alcohol Use Disorder (AUD) patients were compared with 130 healthy controls, with the aim of outlining affective temperament quantity and typology according to the formulation of Akiskal and Mallya. RESULTS: Cyclothymic temperamental quantity differentiated - both at the univariate and multivariate levels - between patients who had various different types of Substance Use Disorder, largely irrespective of the principal substance of abuse (heroin or alcohol); irritable temperament quantity differentiated HUD patients from AUD patients. Hyperthymic temperament typology seemed to be more frequent in healthy controls at both univariate and multivariate levels. LIMITATION: Cross-sectional study. CONCLUSIONS: Our analyses suggest that cyclothymic temperament quantity could best correspond to the temperamental profile of Substance Use Disorder patients independently of principal substance of abuse (alcohol or heroin), and that irritable temperament quantity may differentiate HUD from AUD patients. Hyperthymic temperament typology seemed to be highly protective for HUD and, though a bit less, for AUD patients, and was a typical feature of healthy controls.