Optimisation of pharmacotherapy in psychiatry through therapeutic drug monitoring, molecular brain imaging and pharmacogenetic tests: Focus on antipsychotics.

BACKGROUND: For psychotic disorders (i.e. schizophrenia), pharmacotherapy plays a key role in controlling acute and long-term symptoms. To find the optimal individual dose and dosage strategy, specialised tools are used. Three tools have been proven useful to personalise drug treatments: therapeutic drug monitoring (TDM) of drug levels, pharmacogenetic testing (PG), and molecular neuroimaging. METHODS: In these Guidelines, we provide an in-depth review of pharmacokinetics, pharmacodynamics, and pharmacogenetics for 45 antipsychotics. Over 30 international experts in psychiatry selected studies that have measured drug concentrations in the blood (TDM), gene polymorphisms of enzymes involved in drug metabolism, or receptor/transporter occupancies in the brain (positron emission tomography (PET)). RESULTS: Study results strongly support the use of TDM and the cytochrome P450 (CYP) genotyping and/or phenotyping to guide drug therapies. Evidence-based target ranges are available for titrating drug doses that are often supported by PET findings. CONCLUSION: All three tools discussed in these Guidelines are essential for drug treatment. TDM goes well beyond typical indications such as unclear compliance and polypharmacy. Despite its enormous potential to optimise treatment effects, minimise side effects and ultimately reduce the global burden of diseases, personalised drug treatment has not yet become the standard of care in psychiatry.

Neuropsychiatric Symptoms and Their Association With Sex, Age, and Enzyme Replacement Therapy in Fabry Disease: A Systematic Review.

Patients suffering from Fabry disease (FD) have an increased risk of developing neuropsychiatric symptoms (NPS), mostly impairment in cognitive performance and depression. Single cases of psychosis have been reported, however, their association with FD can be coincidental. Furthermore, deficits in social functioning and adaptation as well as specific coping styles in FD patients were observed. Recent studies focused on a longitudinal course of the disease and identified risk factors associated with specific NPS. Since 2001, enzyme replacement therapy (ERT) has been available and in preliminary studies seems to improve cognitive impairment and adaptive skills. In this systematic review, we analyze the available literature on the NPS in FD and investigate if there are any differences in their distribution between males and females, children/adolescents and adults, and individuals treated with ERT and untreated. We discuss the role of the psychological, environmental, and molecular alterations and their correlation to psychiatric manifestations in FD. Finally, we would like to increase awareness of the spectrum of NPS in FD.

Methylphenidate challenge test in adults with attention deficit/hyperactivity disorder (ADHD): Clinical effects and their predictors.

OBJECTIVE: Adult and children attention deficit/hyperactivity disorder (ADHD) share similar symptoms and responses to drugs such as methylphenidate (MPH). Yet, in Europe, these drugs remain unlicensed for adults. We aimed to assess the effects of an acute MPH challenge on the four dimensions concentration, impulsivity, tension, and general well-being in ADHD adults, and identify predictors of improvement. METHODS: Therapeutic Drug Monitoring was performed to measure MPH plasma levels. A Visual Analogue Scale was administered to patients before and after the acute MPH challenge to measure self-reported changes in the four dimensions. RESULTS: After the acute MPH challenge, our 71 patients showed significant improvement in concentration and tension. The MPH challenge dose correlated with lower patients' age, greater side effects, increased concentration (p = .008) and decreased tension (p = .001). At multiple linear regression MPH plasma levels and absence of postdose side effects predicted concentration improvement, MPH plasma levels predicted tension improvement. MPH plasma levels were significantly higher in patients who reported an improvement in concentration, tension, and impulsivity compared to nonimprovers (p's from .001 to .004). CONCLUSIONS: These findings point to the efficacy of MPH challenge in improving concentration and tension in adult ADHD, thus emphasizing the need for a broader treatment access for these patients.

The Characteristics of Mood Polarity, Temperament, and Suicide Risk in Adult ADHD.

The present study was designed to shed light on a topic rarely explored and to suggest possible ways to detect risk factors for the presence of suicidal ideation and behaviors in a sample of adult patients with Attention-Deficit Hyperactivity Disorder (ADHD). This study also explored the association between ADHD, affective temperaments, the presence of hypomania symptoms, and suicide risk. We hypothesized that (compared to healthy controls) (1) patients with adult ADHD would report more negative affective temperaments and more hypomania symptoms and (2) that they would have a higher suicide risk. The participants included 63 consecutive adult inpatients (18 women, 45 men) with ADHD and 69 healthy controls (42 women, 22 men). All participants were administered the Wender Utah Rating Scale (WURS), the Hypomania Check-List-32 (HCL-32), the Mood Disorder Questionnaire (MDQ), the Temperament Evaluation for Memphis, Pisa, Paris, and San Diego (TEMPS-A), and the Columbia-Suicide Severity Rating Scale (C-SSRS). Forty-six percent of the ADHD patients had an Axis 1 comorbid disorder. ADHD patients (compared to controls) more often reported suicidal ideation (46.0% vs. 5.9%, one-way Fisher exact test p < 0.001; phi = 0.46). ADHD patients and the controls also significantly differed in all the scales administered (with Cohen's d between 0.92-4.70), except for the TEMPS-A Hyperthymia scale. A regression model indicated that ADHD was independently associated with higher scores of a negative temperaments/hypomania factor (Odd Ratio = 14.60) but not with suicidal ideation. A high incidence of suicidal ideation, comorbid psychiatric disorders, and negative affective temperaments was reported in adult ADHD patients, and clinicians should routinely assess risk factors for suicide among these patients.

Suicide risk in attention-deficit/hyperactivity disorder.

BACKGROUND: ADHD (Attention-deficit/hyperactivity disorder) is a common neurodevelopmental disorder that manifests itself during childhood with various combinations of symptoms, including inattention, hyperactivity and impulsivity. Research has shown that psychiatric comorbidities play an important role in the development of suicidal behavior and, recently, there has been a growing interest in a possible association between ADHD and suicide during both childhood and adulthood. Furthermore, some authors have shown a relationship between pharmacological treatments and suicide in patients affected by ADHD. AIMS: We conducted a selective review of current literature to explore the factors which contribute to suicidal behavior and self-harm in those with ADHD. METHODS: We performed a PubMed/MEDLINE, Scopus, PsycLit, and PsycINFO search to identify all articles and book chapters on the topic up to 2017. RESULTS: Several studies have showed that ADHD may be correlated with an increased suicide ideation and attempts. CONCLUSIONS: Although differences in studies design and samples made the results difficult to compare and interpret, many studies indicate an association between ADHD and suicidal behavior. It remains controversial whether there is a direct relationship or whether the association depends on the increased prevalence of pre-existing comorbid conditions and individual and family dysfunctional factors.

[Suicide risk in somatoform disorders]. / Suizidrisiko bei somatoformen Störungen.

BACKGROUND: The somatoform disorders include a group of complex disorders consist of somatic symptoms for which there are no identifiable organic cause or pathogenetic mechanisms. Given the importance of these disorders and the need to clarify the diagnosis of somatoform disorder affecting the suicide risk, we took into consideration the scientific literature to investigate the correlation between the two conditions. METHODS: We performed a bibliographic search through Medline, Embase, PsycINFO, Scopus, SciELO, ORCID, Google Scholar, DOAJ using the following terms: somatoform, somatization disorder, pain disorder AND psychological factor, suicide, parasuicide, suicidality. RESULTS: In all studies reported in our review, the suicidal behavior risk is high. But in the majority, the data are relatively unreliable because it takes into account the category nosographic "Neurotic, stress-related and somatoform disorders", too wide to be able to identify the clinical characteristics of patients at risk of only somatoform disorder. CONCLUSIONS: Several studies conclude that psychiatric comorbidity increases the suicide risk: patients with two or more psychiatric disorders are more likely to commit a suicide attempt; in particular if there is a axis I diagnosis, the risk reduplicate. The somatization disorder seems to have a significant psychiatric comorbidity in particular with anxious and affective disorders spectrum.

[Parkinson's disease and psychoses]. / Parkinson-Krankheit und Psychosen.

Psychotic symptoms are common in Parkinson's disease (PD) and are associated with increased disability, worsened quality of life, and poor long-term prognosis. In this article, clinical features, hypotheses on pathogenesis, and current treatment strategies for Parkinson's disease psychosis (PDP) are reviewed. According to epidemiological studies, the prevalence of PDP is between 20 to 40 %. Complex visual hallucinations are the most common psychotic symptoms and are present in 17-72 % of the patients. Other sensory disturbances encompass tactile hallucinations and minor hallucinatory phenomena, such as sense of presence and visual illusions. Hallucinations are often accompanied by delusions, whose most frequent themes are persecution and jealousy. The pathophysiology of PDP remains unclear. Different factors have been implicated, including Levo-dopa and dopaminergic medications, neurotransmitter imbalances, neuroanatomic alterations, abnormal visuospatial processes, and genetic predisposition. The first-line strategy in the treatment of persistent and problematic PDP is represented by reduction in anti-PD medications. Second-generation antipsychotics are the treatment of choice, with clozapine being demonstrated as the most effective and tolerable drug for PD patients.

[The interaction of Rhodiola rosea and antidepressants. A case report]. / Das Zusammenwirken von Rhodiola rosea (Eisenwurz) und Antidepressiva.

OBJECTIVE: Rhodiola rosea (Russian Rhodiola/Golden Root) is a high mountain plant from the arctic regions of Europe and Asia which has the active substance phenylpropanoide. It has sedative, anti-depressive, drive-enhancing and stress-modulated properties stimulating the distribution of dopamine and serotonin; in combination with other drugs, an increase of side effects and risk profile has to be expected. METHODS: A case report is presented in order to illustrate the interaction between Rhodiola rosea and antidepressants. RESULTS: We report the case of a 68-year-old female patient with recurrent moderate depressive disorder with somatic syndrome (ICD-10 F33.11) who developed vegetative syndrome, restlessness feeling and trembling since she began to ingest Rhodiola rosea in addition to paroxetine. CONCLUSIONS: Prescribing Rhodiola rosea with paroxetine, pharmacokinetic and -dynamic interactions have to be assumed. The symptoms of the patient can be interpreted as a serotonergic syndrome. Because of its different effects, the plant is widely used. An increase of clinical relevant risks should be considered in the add-on treatments.