How COVID-19 Phases Have Impacted Psychiatric Risk: A Retrospective Study in an Emergency Care Unit for Adolescents.

Dramatic events during the COVID-19 pandemic have acutely impacted the psychosocial environment worldwide, with negative implications for mental health, particularly for more vulnerable children and adolescents with severe psychiatric illnesses. Some data suggest that the pandemic waves may have produced different psychopathological consequences, further worsening in the second phase of the pandemic, compared to those in the first lockdown, soon after March 2020. To test the hypothesis of a further worsening of psychiatric consequences of COVID-19 in the second lockdown compared to the first lockdown, we focused our analysis on a consecutive sample of youth referred to a psychiatric emergency unit for acute mental disorders in the time period between March 2019-March 2021. The sample, consisting of 241 subjects (123 males and 118 females, ranging in age from 11 to 17 years), was divided into three groups: Pre-Lockdown Group (PLG, 115 patients); First Lockdown Group (FLG, 65 patients); and Second Lockdown Group (SLG, 61 patients). Patients in the SLG presented more frequently with non-suicidal self-injuries (NSSIs), suicidal ideation, and suicidal behavior, while no significant differences in self-harm were found between PLG and FLG. Eating disorders were more frequent in both the FLG and SLG, compared to the PLG, while sleep problems were higher only in the SLG. Furthermore, patients in the SLG presented with more frequent psychological maltreatments and neglect, as well as with psychiatric disorders in the parents. Adverse traumatic experiences and internalizing disorders were significantly associated with an increased risk of suicidality. Intellectual disability was less represented from the PLG to SLG, and similarly, the rate of ADHD was lower in the SLG. No differences were found for the other psychiatric diagnoses. This information may be helpful for a better understanding and management of adolescents with severe emotional and behavioral disorders after the exposure to long-lasting collective traumas.

Omega-3/6 supplementation for mild to moderate inattentive ADHD: a randomised, double-blind, placebo-controlled efficacy study in Italian children.

Recently there has been a growing interest in non-pharmacological treatments for ADHD. We evaluated the efficacy of a specific Omega-3/6 dietary supplement (two capsules containing 279 mg eicosapentaenoic acid [EPA], 87 mg Docosahexaenoic Acid [DHA], 30 mg gamma linolenic acid [GLA] each) in ameliorating inattentive symptoms in inattentive-ADHD children (6-12 years) with a baseline ADHD-RS-Inattention score ≥ 12. Secondary objectives included changes in global functioning, severity of illness, depression, and anxiety symptoms, learning disorders and in the fatty acids blood levels. The study was a randomised, double-blind, placebo-controlled efficacy and safety trial with a 6-month double-blind evaluation of Omega-3/6 vs placebo (Phase-I) and a further 6-month-open-label treatment with Omega-3/6 on all patients (Phase-II). In total 160 subjects were enrolled. No superiority of Omega-3/6 supplement to placebo was observed on the primary outcome (ADHD-RS-inattention score) after the first 6-months, with 46.3% of responders in the Omega-3/6 group and 45.6% in the placebo group; a slight (not statistically significant) reduction in Omega-6/3 ratio blood levels was measured in the active treatment group. Twelve months after enrolment, percentages of responders were similar between groups. A mild statistical, although not clinically significant, improvement was observed on the ADHD-RS-total score in the Omega-3/6 group but not on the ADHD-RS-Inattention score; a slight (not-statistically significant) reduction in Omega-6/3 ratio was observed in the group taking active treatment only during Phase II. In conclusion, no clinical beneficial effects of Omega-3/6 were detected on inattentive symptoms, suggesting a limited role of Omega-3/6 dietary products in children with mild ADHD-I.Trial registration: At the time of the Ethical submission, according to the clinical trial Italian law, registration was not mandatory for food additive as Omega 3/6 were then classified. The trial was approved by the Ethical Committee of the Cagliari University Hospital (resolution n. 662; September 22nd, 2011).

Acute Tolerability of Methylphenidate in Treatment-Naïve Children with ADHD: An Analysis of Naturalistically Collected Data from Clinical Practice.

OBJECTIVES: The acute tolerability of methylphenidate (MPH) in children with attention-deficit/hyperactivity disorder (ADHD) has been studied mainly in research samples. Taking advantage of the mandatory test-dose procedure required for starting MPH in Italy, this study aimed to assess the incidence of intolerable adverse events after initial exposure to MPH in routine clinical practice. METHODS: The medical records of 480 consecutively treated, previously drug-naïve children and adolescents with ADHD (90% male, mean age 10.6 ± 3.0 years) were retrospectively analyzed. All children received an initial single dose of MPH immediate release (5 or 10 mg) followed by a 4-hour direct medical observation. Heart rate and blood pressure were measured at dosing and 1, 2, and 3 hours afterwards. If the first dose was well tolerated, the child continued treatment with MPH 5-20 mg daily, and was reassessed a week later. RESULTS: Eleven patients (2.3%, 95% CI 1.1-4.1) interrupted treatment within a week of initiation because of the following adverse events: irritability (n = 3), tics worsening (n = 3), reduced appetite (n = 1), enuresis (n = 1), hallucinations (n = 1), hyperfocus (n = 1), and 'rebound' behavioral worsening (n = 1). The most common adverse events were reduced appetite (20%), irritability (14.2%), headache (10.6%), sleep problems (9.4%), stomachache (9.4%), and tics (5%). Intellectual disability increased the risk of any adverse event in general and of irritability in particular. No cardiovascular symptom was clinically reported. However, routine assessments of vital signs during the first 3 hours after the first dose of MPH showed that 9% of the children had a 20% increase in heart rate, 8.8% had a 20% increase in diastolic blood pressure and 4.5% had a 20% increase in systolic blood pressure. Of these, 25.2% still had an elevated heart rate 1 week later. CONCLUSIONS: Among stimulant-naïve children in clinical practice, the incidence of acute MPH intolerance can be estimated to be between 1.2 and 4.1%. An asymptomatic elevation in cardiovascular parameters can be observed in about 1 out of 10 children and warrants monitoring during ongoing treatment.

A Naturalistic Study of Youth Referred to a Tertiary Care Facility for Acute Hypomanic or Manic Episode.

BACKGROUND: Bipolar Disorders (BD) in youth are a heterogeneous condition with different phenomenology, patterns of comorbidity and outcomes. Our aim was to explore the effects of gender; age at onset (prepubertal- vs. adolescent-onset) of BD; and elements associated with attention deficit hyperactivity disorder (ADHD) and Substance Use Disorder (SUD) comorbidities, severe suicidal ideation or attempts, and poorer response to pharmacological treatments. METHOD: 117 youth (69 males and 57 females, age range 7 to 18 years, mean age 14.5 ± 2.6 years) consecutively referred for (hypo)manic episodes according to the Diagnostic and Statistical Manual of Mental Disorders, 54th ed (DSM 5) were included. RESULTS: Gender differences were not evident for any of the selected features. Prepubertal-onset BD was associated with higher rates of ADHD and externalizing disorders. SUD was higher in adolescent-onset BD and was associated with externalizing comorbidities and lower response to treatments. None of the selected measures differentiated patients with or without suicidality. At a 6-month follow up, 51.3% of the patients were responders to treatments, without difference between those receiving and not receiving a psychotherapy. Clinical severity at baseline and comorbidity with Conduct Disorder (CD) and SUD were associated with poorer response. Logistic regression indicated that baseline severity and number of externalizing disorders were associated with a poorer outcome. CONCLUSIONS: Disentangling broader clinical conditions in more specific phenotypes can help timely and focused preventative and therapeutic interventions.

A NATURALISTIC EXPLORATORY STUDY OF OBSESSIVE-COMPULSIVE BIPOLAR COMORBIDITY IN YOUTH.

BACKGROUND: Growing evidence supports the comorbidity between bipolar disorder (BD) and obsessive-compulsive disorder (OCD) in children and adolescents. Our aim is to further explore clinical and treatment implications of this comorbidity, as it appears in clinical practice. METHOD: The sample included 429 consecutive patients with BD and/or OCD as primary diagnoses, followed for a mean period of 6 months (range 4-9 months), 172 with BD (102 males, mean age 13.7±2.9 years), 169 with OCD (118 males, mean age of 13.2±2.7 years) and 88 with comorbid BD+OCD (56 males, mean age 14.2±2.6 years, 52 with BD as the primary diagnosis), followed for a mean period of 6 months (range 4-9 months). The comorbid group was compared to pure BD and OCD groups, to explore differential clinical and treatment features. RESULTS: The BD-OCD comorbidity was found in 33.8% of the BD patients and in 34.2% of the OCD patients. Age at onset of BD and OCD were not different in pure and "comorbid" groups. The comorbid group presented a higher occurrence of BD type II and hoarding symptoms, and more frequently received a psychotherapy and second generation antipsychotics, but it presented the poorest outcome in terms of response to treatments. Severity at baseline (clinical severity and functional impairment), hoarding obsessions and compulsions, and conduct disorder comorbidity were associated with a treatment non-response. LIMITATIONS: A selection bias may have increased the rate of comorbidity, as most of the patients were referred to our tertiary hospital for severe BD and/or OCD and pharmacological treatment. We have used CGI-I as an outcome measure, not a specific measure of BD or OCD symptoms' severity and improvement. The short duration of the follow-up may limit our conclusions. CONCLUSIONS: The timely identification of BD-OCD comorbidity may have relevant clinical implications in terms of symptomatology, course, treatment and outcome.

Management of schizophrenia in children and adolescents: focus on pharmacotherapy.

Schizophrenia in subjects younger than 13 years is defined as very-early-onset schizophrenia, and its prevalence is estimated at 1 in 10 000, while early-onset schizophrenia occurs between 13 and 17 years, and its prevalence is about 0.5%. Only a minority of youths show a complete recovery, and the majority of patients present a moderate to severe impairment at the outset. Treatment of schizophrenia always needs both pharmacological and nonpharmacological interventions. Nonpharmacological interventions include counselling for the patients and the family, psychological support, behavioural treatments, social and cognitive rehabilitation, assistance in social and scholastic activities, enhancement of social skills and family support. Pharmacological treatment is necessary for remission and control of positive and negative symptoms. Furthermore, proper pharmacotherapy can greatly increase the efficacy of psychosocial interventions. Available literature on pharmacotherapy in children and adolescents with schizophrenia is critically reviewed, including both first- and second-generation antipsychotics. Data on efficacy and safety are reported for all the marketed atypical antipsychotics (clozapine, risperidone, olanzapine, quetiapine, ziprasidone and aripiprazole), based on randomized, placebo-controlled studies and the most relevant open-label or naturalistic studies. Adverse effects of concern are closely analysed, such as extrapyramidal side effects and tardive dyskinesia, metabolic syndrome (including hyperglycaemia and hyperlipidaemia), weight gain, hyperprolactinaemia, hepatotoxicity, seizures, and cardiovascular and haematological adverse effects. Finally, practical guidelines for the management of specific clinical situations are provided: the first phases and the long-term approach to pharmacotherapy, the treatment refractoriness and the use of clozapine in youths, the agitated adolescent and the treatment of negative symptoms and of affective co-morbidity. Current experience indicates that, based on low rates of remission, low effect size of medications and frequent adverse effects, mainly metabolic syndrome, further research is warranted, with both randomized, placebo-controlled studies and long-term, naturalistic follow-up of large samples of patients with different age ranges.

Pharmacotherapy of major depressive disorder in adolescents.

IMPORTANCE OF THE FIELD: At any one time, major depressive disorder (MDD) affects 4 - 6% of adolescents. When untreated, MDD leads to a high immediate and subsequent suicide risk, long-term chronicity and a poor psychosocial outcome. Whereas psychotherapy can be effective in mild depression, it seems to be less effective in moderate and severe depression. However, although the use of antidepressants increased markedly during the 1990s, in recent years it has decreased as a result of concerns regarding the emergence of suicidality during antidepressant treatment. AREAS COVERED IN THIS REVIEW: Are antidepressants truly effective? What is the relationship between different treatments for depression - psychotherapy and pharmacotherapy - alone or in combination? Can antidepressants increase the risk of suicide in some adolescents? Can antidepressants reduce suicide risk in suicidal adolescents? WHAT THE READER WILL GAIN: There is evidence that selective serotonin reuptake inhibitors (SSRIs) can improve adolescent depression better than placebo, although the magnitude of the antidepressant effect is 'small to moderate', because of a high placebo response. The SSRI with the best rate of response compared to placebo is fluoxetine. The increased risk of suicidality in adolescents, compared to adults, is weak but consistent across most studies. However, epidemiological studies do not support a relationship between use of antidepressants and suicide rate. TAKE HOME MESSAGE: A cautious and well-monitored use of antidepressant medications is a first-line treatment option in adolescents with moderate to severe depression. Low rates of remission with current treatment strategies indicate that further research in both psychotherapy and pharmacotherapy is warranted.