Pitfalls in Adolescent Psychiatry

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Master of Isabella di Chiaromonte, Matteo Felice (illuminators), David with musicians and dancing children, marked as public domain, more details on Wikimedia Commons

 

In his article Thyroid, Insomnia, and the Insanities: Commonalities in Disease, Dr. Raymond Peat, PhD talks about the chronology of mental illness:

“Stress damages the energy producing systems of cells, especially the aerobic mitochondria, in many ways, and this damage can often be repaired. The insanities that are most often called schizophrenia tend to occur in late adolescence, or around menopause, or in old age, which are times of stress, especially hormonal stress. Post-partum psychosis often has features that resemble schizophrenia.”

Mental illnesses often appear in the early years of one’s life:

“There is mounting evidence that many, if not most, lifetime psychiatric disorders will first appear in childhood or adolescence. Methods are now available to monitor youths and to make early intervention feasible.”

Up to 1 in 20 children under the age of 18 suffer from depression, particularly girls:

“Unipolar depressive disorder in adolescence is common worldwide but often unrecognised. The incidence, notably in girls, rises sharply after puberty and, by the end of adolescence, the 1 year prevalence rate exceeds 4%.”

The average age of admittance in the psych ward coalesced with the beginning stages of late adolescence:

“Mean age at the index admission and the follow-up was 16.6 ± 1.2 and 24.5 ± 3.0 years respectively.”

An assessment of adolescents in psych wards reveals a release of almost all admitted persons, but also a a readmission of the majority of patients, indicative of the failure of emergency psychiatric institutions.

“After the subsequent discharge almost all subjects (97%) at least briefly continued psychiatric treatment and 75% of patients had been readmitted.”

The term “diagnostic stability” refers to the recurrence of symptoms for a given diagnosis.  If half of all patients originally diagnosed with symptoms of borderline personality disorder later have symptoms more in line with bipolar disorder, then the diagnostic stability would be only 50%.

Psychiatric diagnoses remain constant less than half of the time:

“Overall diagnostic stability was 42%. For schizophrenia spectrum disorders and schizophrenia diagnostic stability was 72% and 78%, respectively. At the follow-up assessment 119 (77.3%) of the traced subjects declared current psychiatric treatment and 110 (73.3%) were receiving pharmacotherapy. Almost half of the subjects (48%) were employed or studying and more than a third (35.8%) remained in a stable relationship. Different distributions of baseline diagnoses were observed in males and females, and the latter showed a better outcome.”

Except for fluoxetine (Prozac), the majority of antidepressants fail to treat depression in adolescents:

“We deemed 34 trials eligible, including 5260 participants and 14 antidepressant treatments.  For efficacy, only fluoxetine was statistically significantly more effective than placebo.”

Some antidepressants worsened the state of patients with side effects:

“Patients given imipramine, venlafaxine, and duloxetine had more discontinuations due to adverse events than did those given placebo”

References

Costello, E. J., Egger, H., & Angold, A. (2005). 10-year research update review: the epidemiology of child and adolescent psychiatric disorders: I. Methods and public health burden. Journal of the American Academy of Child and Adolescent Psychiatry, 44(10), 972–986. https://doi.org/10.1097/01.chi.0000172552.41596.6f
OBJECTIVE: To review recent progress in child and adolescent psychiatric epidemiology in the area of prevalence and burden. METHOD: The literature published in the past decade was reviewed under two headings: methods and findings. RESULTS: Methods for assessing the prevalence and community burden of child and adolescent psychiatric disorders have improved dramatically in the past decade. There are now available a broad range of interviews that generate DSM and ICD diagnoses with good reliability and validity. Clinicians and researchers can choose among interview styles (respondent based, interviewer based, best estimate) and methods of data collection (paper and pencil, computer assisted, interviewer or self-completion) that best meet their needs. Work is also in progress to develop brief screens to identify children in need of more detailed assessment, for use by teachers, pediatricians, and other professionals. The median prevalence estimate of functionally impairing child and adolescent psychiatric disorders is 12%, although the range of estimates is wide. Disorders that often appear first in childhood or adolescence are among those ranked highest in the World Health Organization’s estimates of the global burden of disease. CONCLUSIONS: There is mounting evidence that many, if not most, lifetime psychiatric disorders will first appear in childhood or adolescence. Methods are now available to monitor youths and to make early intervention feasible.

Cipriani, A., Zhou, X., Giovane, C. D., Hetrick, S. E., Qin, B., Whittington, C., … Xie, P. (2016). Comparative efficacy and tolerability of antidepressants for major depressive disorder in children and adolescents: a network meta-analysis. The Lancet, 388(10047), 881–890. https://doi.org/10.1016/S0140-6736(16)30385-3

Summary

Background

Major depressive disorder is one of the most common mental disorders in children and adolescents. However, whether to use pharmacological interventions in this population and which drug should be preferred are still matters of controversy. Consequently, we aimed to compare and rank antidepressants and placebo for major depressive disorder in young people.

Methods

We did a network meta-analysis to identify both direct and indirect evidence from relevant trials. We searched PubMed, the Cochrane Library, Web of Science, Embase, CINAHL, PsycINFO, LiLACS, regulatory agencies’ websites, and international registers for published and unpublished, double-blind randomised controlled trials up to May 31, 2015, for the acute treatment of major depressive disorder in children and adolescents. We included trials of amitriptyline, citalopram, clomipramine, desipramine, duloxetine, escitalopram, fluoxetine, imipramine, mirtazapine, nefazodone, nortriptyline, paroxetine, sertraline, and venlafaxine. Trials recruiting participants with treatment-resistant depression, treatment duration of less than 4 weeks, or an overall sample size of less than ten patients were excluded. We extracted the relevant information from the published reports with a predefined data extraction sheet, and assessed the risk of bias with the Cochrane risk of bias tool. The primary outcomes were efficacy (change in depressive symptoms) and tolerability (discontinuations due to adverse events). We did pair-wise meta-analyses using the random-effects model and then did a random-effects network meta-analysis within a Bayesian framework. We assessed the quality of evidence contributing to each network estimate using the GRADE framework. This study is registered with PROSPERO, number CRD42015016023.

Findings

We deemed 34 trials eligible, including 5260 participants and 14 antidepressant treatments. The quality of evidence was rated as very low in most comparisons. For efficacy, only fluoxetine was statistically significantly more effective than placebo (standardised mean difference −0·51, 95% credible interval [CrI] −0·99 to −0·03). In terms of tolerability, fluoxetine was also better than duloxetine (odds ratio [OR] 0·31, 95% CrI 0·13 to 0·95) and imipramine (0·23, 0·04 to 0·78). Patients given imipramine, venlafaxine, and duloxetine had more discontinuations due to adverse events than did those given placebo (5·49, 1·96 to 20·86; 3·19, 1·01 to 18·70; and 2·80, 1·20 to 9·42, respectively). In terms of heterogeneity, the global I2 values were 33·21% for efficacy and 0% for tolerability.

Interpretation

When considering the risk–benefit profile of antidepressants in the acute treatment of major depressive disorder, these drugs do not seem to offer a clear advantage for children and adolescents. Fluoxetine is probably the best option to consider when a pharmacological treatment is indicated.

Funding

National Basic Research Program of China (973 Program).

 Raymond Peat, PhD. (2009). Thyroid, insomnia, and the insanities: Commonalities in disease. Retrieved September 13, 2017, from http://raypeat.com/articles/articles/thyroid-insanities.shtml 

Remberk, B., Bażyńska, A. K., Krempa-Kowalewska, A., & Rybakowski, F. (2014). Adolescent insanity revisited: course and outcome in early-onset schizophrenia spectrum psychoses in an 8-year follow-up study. Comprehensive Psychiatry, 55(5), 1174–1181. https://doi.org/10.1016/j.comppsych.2014.03.013
OBJECTIVES: Despite inclusion of adolescent insanity-a concept proposed by Thomas Clouston in late XIX century-into the broader nosological entity of dementia praecox, the uniqueness of early psychosis is still discussed. The aim of the current study is the assessment of course and outcome in the large sample of early-onset psychosis subjects. METHOD: Of 299 patients hospitalized in the period 1998-2008 in an adolescent psychiatry ward with schizophrenia spectrum diagnosis 158 completed a follow-up interview. Data concerning current diagnosis, further admissions, current treatment status and occupational and relationship outcome were analyzed after a mean of 8 years of follow-up. RESULTS: Mean age at the index admission and the follow-up was 16.6 ± 1.2 and 24.5 ± 3.0 years respectively. After the subsequent discharge almost all subjects (97%) at least briefly continued psychiatric treatment and 75% of patients had been readmitted. Overall diagnostic stability was 42%. For schizophrenia spectrum disorders and schizophrenia diagnostic stability was 72% and 78%, respectively. At the follow-up assessment 119 (77.3%) of the traced subjects declared current psychiatric treatment and 110 (73.3%) were receiving pharmacotherapy. Almost half of the subjects (48%) were employed or studying and more than a third (35.8%) remained in a stable relationship. Different distributions of baseline diagnoses were observed in males and females, and the latter showed a better outcome. CONCLUSION: Early-onset psychoses were characterized by limited diagnostic stability, a necessity for further treatment and hospitalizations and significant percentage of unfavorable functional outcomes. Baseline diagnosis of acute and transient psychotic disorders and female gender were associated with an overall better outcome.

Remberk, B., Bażyńska, A. K., Bronowska, Z., Potocki, P., Krempa-Kowalewska, A., Niwiński, P., & Rybakowski, F. (2015). Which aspects of long-term outcome are predicted by positive and negative symptoms in early-onset psychosis? An exploratory eight-year follow-up study. Psychopathology, 48(1), 47–55. https://doi.org/10.1159/000366489
BACKGROUND: Early-onset psychoses show substantial variability of diagnostic and functional outcome. Finding reliable prognostic factors may allow to allocate resources to those with the worst prognosis. The aim of the study was to gain new insights regarding the potential value of baseline negative and positive symptoms as predictors of outcome in psychoses of early onset. METHOD: Sixty-three patients with early-onset schizophrenia spectrum psychosis hospitalized in an adolescent psychiatry unit were assessed with the Positive and Negative Syndrome Scale during the index admission. Associations with diagnosis, illness course and functional outcome were analysed in mean 8 years of follow-up (range 3.4-13.5 years). RESULTS: The mean age at the index admission and the follow-up was 16.6 ± 1.2 and 24.5 ± 3.0 years, respectively. A significant majority of subjects continued psychiatric treatment (95%) and had been readmitted (71%). The mortality rate was 3% (suicide and accident). Negative symptoms were related to mental health service utilization during the follow-up. General severity of symptoms, specifically positive and cognitive factors were associated with the diagnosis of schizophrenia and inversely with diagnostic shift outside the schizophrenia spectrum at the catamnesis. Poor impulse control at baseline was associated with worse functional outcome. The drug-free subgroup with no occupational/educational activity compared with the drug-treated subjects showed lower levels of baseline negative symptomatology. CONCLUSION: The study findings suggest that in patients with early-onset psychosis negative and positive symptoms show a differential prognostic value. Pharmacotherapy may attenuate the effect of symptoms on functional outcome. These hypotheses need to be tested in future studies using confirmatory approaches.

Thapar, A., Collishaw, S., Pine, D. S., & Thapar, A. K. (2012). Depression in adolescence. Lancet, 379(9820), 1056–1067. https://doi.org/10.1016/S0140-6736(11)60871-4
Unipolar depressive disorder in adolescence is common worldwide but often unrecognised. The incidence, notably in girls, rises sharply after puberty and, by the end of adolescence, the 1 year prevalence rate exceeds 4%. The burden is highest in low-income and middle-income countries. Depression is associated with sub stantial present and future morbidity, and heightens suicide risk. The strongest risk factors for depression in adolescents are a family history of depression and exposure to psychosocial stress. Inherited risks, developmental factors, sex hormones, and psychosocial adversity interact to increase risk through hormonal factors and associated perturbed neural pathways. Although many similarities between depression in adolescence and depression in adulthood exist, in adolescents the use of antidepressants is of concern and opinions about clinical management are divided. Effective treatments are available, but choices are dependent on depression severity and available resources. Prevention strategies targeted at high-risk groups are promising.

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