Assessment of the association between non-suicidal self-injury disorder and suicidal behaviour disorder in females with conduct disorder.

BACKGROUND: Non-suicidal self-injury (NSSI) and aggression have been demonstrated to serve as risk factors of suicidal behaviours (SB). Non-suicidal self-injury disorder (NSSID) and Suicidal Behaviour Disorder (SBD) are among new diagnostic categories for further studies in the DSM-5 classification. METHODS: We recruited 196 girls (aged 15.5 ± 1.2 years) diagnosed with conduct disorder (CD). All of them were assessed with respect of non-suicidal self-injury acts, suicidal attempts, psychopathology, self-esteem and general functioning. RESULTS: Age of NSSI onset was significantly lower compared to age of first suicidal attempt. SBD was present in 50.0% of patients with NSSID and the prevalence of NSSID in individuals with SBD was estimated at 52.2%. A diagnosis of NSSID, with at least 8 days of engagement in self-injuries during the preceding year, significantly predicted the risk of SBD. This effect appeared to be independent of depressive symptomatology. LIMITATIONS: Our results cannot be generalized over the whole population of individuals diagnosed with CD because of a lack of male patients, as well as individuals with the most severe and mildest forms of CD. Causal inferences cannot be established due to a cross-sectional study design. CONCLUSIONS: The NSSID with at least 8 days of engagement in self-injuries during the preceding year serves as a predictor of SBD independently of the effects of depressive symptoms. Longitudinal studies are required to confirm our findings.

Profiling inflammatory signatures of schizophrenia: A cross-sectional and meta-analysis study.

We aimed to profile a broad panel of inflammatory markers in patients with schizophrenia and healthy controls. Additionally, we performed a meta-analysis of chemokine alterations that have not been subjected to quantitative synthesis so far. We recruited 78 patients with schizophrenia and 78 healthy controls, and measured inflammatory markers using the Luminex technology. After adjustment for multiple testing, we found elevated levels of interleukin (IL)-1 receptor antagonist (IL-1RA), IL-6, IL-7, IL-8, IL-9, IL-10, IL-13, interferon-γ, eotaxin-1, granulocyte-macrophage colony-stimulating factor (GM-CSF), monocyte chemoattractant protein-1 (MCP-1), platelet-derived growth factor with two B subunits (PDGF-BB), macrophage inflammatory protein (MIP)-1α, MIP-1ß, vascular endothelial growth factor A (VEGF-A) and RANTES in multiple-episode schizophrenia (MES) patients. These differences, except for the difference in eotaxin-1 levels, appeared to be significant after co-varying for the dosage of antipsychotics. There were no significant differences in the levels of immune markers between first-episode schizophrenia (FES) patients and controls. Our meta-analysis revealed elevated levels of MCP-1 in first-episode psychosis (FEP) patients and MES individuals. Other chemokine alterations (elevated levels of IL-8, eotaxin-1 and MIP-1ß) were present only in MES patients. Our results indicate that dysregulation of immune response in schizophrenia develops with illness progression or appears as a long-term medication effect. Chemokine alterations are another example of aberrant immune response in schizophrenia patients. Elevated levels of MCP-1 might represent trait markers since these alterations were found in FEP and MES patients. Other chemokine alterations might be the markers of disease progression or might represent medication effects.

Not all drugs are created equal: impaired future thinking in opiate, but not alcohol, users.

Episodic future thinking refers to the ability to travel forward in time to pre-experience an event. Although future thinking has been intimately linked with self and identity, to our knowledge, no prior research has compared episodic future thinking in populations with different substance use disorders. This study investigates whether there are differences in episodic future thinking between these alcohol and opiate users. The study recruited participants who were on the opiate substitution program (n = 31) and individuals who had been diagnosed with alcohol dependence (n = 21) from the Royal Prince Alfred Hospital Drug and Health Services. Healthy controls (n = 23) were recruited via Royal Prince Alfred Hospital databases and the general community. Past and future thinking was measured using four cue words. After each cue word, participants rated their phenomenological experience (e.g. emotion, reliving experience). Results indicated that alcohol-dependent individuals performed significantly higher in episodic future thinking compared to opiate users. These findings indicate that not all substance use disorder groups share similar episodic thinking capabilities. Our results suggest that the self-projection component of rehabilitation programs may have to be tailored to the different episodic construction abilities found in substance use disorder groups.

CTLA4 and CD28 Gene Polymorphisms with Respect to Affective Symptom Domain in Schizophrenia.

BACKGROUND: Accumulating evidence indicates that immune alterations in schizophrenia are due to genetic underpinnings. Here, we aimed at investigating whether polymorphisms in CTLA4 and CD28 genes, encoding molecules that regulate T-cell activity, influence schizophrenia symptomatology. METHOD: We recruited 120 schizophrenia patients and 380 healthy age- and sex-matched controls. We divided the patients into two groups: one with no co-occurrence between psychotic and affective symptoms and the second one with psychotic symptoms dominating in the clinical manifestation, although also with occasional affective disturbances in the course of illness. RESULTS: Among the patients with co-occurring affective symptoms, there were significantly more CTLA4 c.49A>G[A] alleles (p = 0.018, odds ratio (OR) 2.03, 95% confidence interval (CI) 1.2-3.66) and more CTLA4 g.319C>T[T] alleles (p = 0.07, OR 1.93, 95% CI 0.94-4.13) in comparison to the second group. Additionally, we have shown that CD28 c.17 + 3T>C[C+] were more significantly overrepresented among patients with co-occurring psychotic and affective symptoms (p = 0.0003, OR 3.36, 95% CI 1.69-6.68) than in patients without co-occurence between these symptoms (p = 0.012, OR 1.88, 95% CI 1.15-3.10). CONCLUSION: CTLA4 and CD28 gene polymorphisms may not only act in immune deregulation observed in schizophrenia, but may also influence the course of the illness by modifying the susceptibility to the co-occurrence of psychotic and affective symptoms.

[The study of the Polish version of the Questionnaire for the Assessment of Disgust Sensitivity (QADS)]. / Polskie badania nad Kwestionariuszem Oceny Wrazliwosci na Wstret (QADS).

AIM: Disgust is one of the principal emotions, typically triggered by a variety of biological and social stimuli. Several questionnaire tools have been used to assess disgust. The aim of the study was to assess psychometric properties of the Polish version of the Questionnaire for the Assessment of Disgust Sensitivity (QADS), adapted from the tool prepared by the German researchers. METHODS: Eight hundred twenty subjects (631, 77% females and 189, 23% males) aged 18-69 (mean - 28 years) participated in the study. There are 3 subscale in the questionnaire: Core Disgust, Animal Reminder and Contamination. The tool consists of 37 items, the intensity of feeling of disgust is assessed based on 5-point Likert scale. RESULTS: Confirmatory factor analysis confirmed the adequacy of grouping of items in the three subscales: Core Disgust, Animal-Reminder, and Contamination-Interpersonal. In our sample, females had higher levels of disgust than males. Several other psychometric variables - high degree of correlations between the subscales, and high reliability -were in agreement with parameters of the original version. The Polish version compared favourably with the original, with Cronbach's alpha of 0.94 for the whole questionnaire and 0.85 - 0.90 for the subscales. CONCLUSIONS: The psychometric properties of the Polish version of QADS are sufficient to recommend this tool for diagnostic and research use.

[Will new diagnostic criteria facilitate the diagnostic process of ADHD in adults?]. / Czy zmiana kryteriów diagnostycznych ulatwi rozpoznanie ADHD u doroslych?

ADHD is traditionally described as a pediatric disorder. According to contemporary knowledge in around 60% of children suffering from ADHD symptoms of the disorder persist into adulthood. The epidemiological data show the 2-5% prevalence ofADHD in adults. The consequences of the disorder are serious and may cause other health problems and impairments in occupational and individual functioning. The diagnosis ofADHD in adult is based on diagnostic criteria which were created for children. As a result, many difficulties and doubts appear during diagnostic process, and it may also lead to underdiagnosis ofADHD in adults. The paper presents disadvantages of the current diagnostic criteria of ADHD in adults in both DSM-IV and ICD-10. Suggestions of authorities concerning the changes, which may facilitate the diagnosis of ADHD were discussed. The most important proposals are: with reference to symptoms - the inclusion of additional symptoms describing the specificity of hyperactivity in adults and the reduction of number of symptoms, which should be fulfilled to set the diagnosis; with reference to age-onset criterion - the increase of age level (symptoms should begin before 12).

Unraveling the complexity of associations between a history of childhood trauma, psychotic-like experiences, depression and non-suicidal self-injury: A network analysis.

BACKGROUND: Several studies have reported the association of psychotic-like experiences (PLEs) with non-suicidal self-injury (NSSI). It has been hypothesized that both constructs might share overlapping backgrounds. This study aimed to investigate the relationships between childhood trauma, depression, PLEs and lifetime characteristics of NSSI. METHODS: Participants included individuals aged 18-35 years who had a negative history of psychiatric treatment. They were surveyed through the computer-assisted web interview. A network analysis was performed. RESULTS: A total of 4203 non-clinical adults (63.8 % females) were enrolled. The characteristics of NSSI and a history of childhood sexual abuse were the most central nodes in the network. A history of childhood sexual abuse was the only category of childhood trauma that was directly connected to the characteristics of NSSI (i.e., longer lifetime duration of NSSI). The shortest pathways from other categories of childhood trauma (emotional abuse, emotional neglect and bullying) were connected to the lifetime characteristics through the effects of sexual abuse. However, other pathways were also possible and converged on nodes representing persecutory thoughts, déjàvu experiences, psychomotor retardation/agitation and suicidal ideation. These psychopathological symptoms were the only nodes directly connected to the characteristics of NSSI (i.e., lifetime duration and a history of severe NSSI). LIMITATIONS: The main limitations include the use of a non-clinical sample and cross-sectional design. CONCLUSIONS: Our findings do not support the hypothesis that PLEs and NSSI might be associated due to shared correlates. In other words, the associations of childhood trauma and PLEs with NSSI might be independent.

Adverse childhood experiences and low socioeconomic status with respect to allostatic load in adulthood: A systematic review.

Early-life psychosocial stress primes a number of health risk behaviors, and contributes to the development of various mental and somatic disorders in adulthood. It has been reported that adverse childhood experiences (ACEs) and low socioeconomic status (SES) might be associated with allostatic load (AL) in adulthood. In turn, elevated AL index has been found to predict a number of unfavorable health outcomes. Therefore, we aimed to perform a systematic review of studies investigating the association of ACEs and childhood SES with AL in adult populations. Independent online searches covered the publication period up to 20th Jun 2021. A total of 27 studies were included in qualitative synthesis. The majority of eligible studies showed that ACEs (14 out of 19 studies recording ACEs, 73.7%) and low childhood SES (11 out of 12 studies recording childhood SES, 91.7%) are associated with elevated AL in adults. However, several processes were found to mediate or moderate this association. These include educational attainments, social support, health behaviors, adult stress, post-traumatic stress disorder, coping strategies and aging. Moreover, a substantial methodological heterogeneity of approaches to calculating the AL index was observed. Apart from reports from overlapping samples, none of eligible studies used the same set of biomarkers. Findings from this systematic review imply that early-life psychosocial stress might have a lasting impact on biological dysregulations captured by the AL index. Future studies need to explore whether the association between early-life stress and the AL index accounts for the development of specific health outcomes.

Self-Injuries and Their Functions with Respect to Suicide Risk in Adolescents with Conduct Disorder: Findings from a Path Analysis.

Non-suicidal self-injuries (NSSIs) have been identified as one of the most predictive factors of suicidal behaviours in adolescents. However, it remains unknown whether certain functions of NSSIs are associated with suicide risk, and what are the underlying mechanisms. Therefore, we aimed to investigate the association between functions of NSSIs and suicide risk in adolescents with conduct disorder (CD), which shares some common characteristics with NSSIs. Participants were 215 adolescents (155 females, 72.1%) with CD. Functions of NSSIs, depressive symptoms, the levels of impulsivity, anxiety, self-esteem and aggression were examined. There were 77 adolescents with lifetime history of NSSIs (35.8%). Among them, adolescents with lifetime history of suicide attempt were significantly more likely to report anti-dissociation and anti-suicide function of NSSIs. They had significantly higher levels of anxiety as well as significantly lower self-esteem. Higher lifetime number of NSSIs was associated with higher odds of reporting anti-dissociation and anti-suicide functions. Moreover, these two functions fully mediated the association between lifetime number of NSSIs and suicide risk after co-varying for depressive and anxiety symptoms as well as self-esteem. The present findings indicate that anti-suicide and anti-dissociation functions of NSSIs might be crucial predictors of suicide risk in adolescents with CD.

From Emotional Intelligence to Self-Injuries: A Path Analysis in Adolescents With Conduct Disorder.

Objective: Self-harm acts are highly prevalent among adolescents with conduct disorder. It has been shown that low level of emotional intelligence (EI) might be related to a higher risk of self-injuries. However, the exact mechanisms underlying this association are still unclear. The purpose of this study was to explore whether psychopathological symptoms and selected psychological processes mediate the association between EI and self-harm risk in adolescents with conduct disorders. Method: Out of 162 adolescents with conduct disorder approached for participation, 136 individuals (aged 14.8 ± 1.2 years, 56.6% females) were enrolled and completed the questionnaires evaluating the level of EI, depression, anxiety, impulsiveness, empathy, venturesomeness, self-esteem, and disgust. Results: Individuals with a lifetime history of self-injuries had significantly higher levels of depression, anxiety and impulsivity as well as significantly lower levels of EI and self-esteem. Higher levels of EI were associated with significantly higher levels of self-esteem, venturesomeness and empathy as well as significantly lower levels of depression, anxiety and impulsivity. Further analysis revealed that trait and state anxiety as well as self-esteem were complete mediators of the association between EI and self-harm risk. Conclusions: Our findings indicate that anxiety and self-esteem might mediate the association between EI and a risk of self-injuries in adolescents with conduct disorder. However, a cross-sectional design of this study limits conclusions on the direction of causality. Longitudinal studies are needed to test validity of our model.

[Infection or allergic reaction to carbamazepine? Diagnostic complications]. / Choroba zakazna czy reakcja alergiczna na karbamazepine? Trudnosci diagnostyczne.

The paper presents the case report of a patient diagnosed with borderline personality disorder, treated with carbamazepine. During the treatment symptoms of the infection of upper respiratory tract appeared, which evolved to allergic symptoms and then to morbilli-like and mumps-like symptoms. The patient was hospitalized due to this disorder for two weeks, in the beginning on an isolation ward and then was diagnosed and treated on a dermatological ward. The diagnosis of the disorder was doubtful due to polymorphic symptoms and their evolution. Detailed course of the disease, diagnostic process and laboratory results were presented in the case report. The authors also attempt to classify these symptoms and to analyse the relationship between the observed symptoms and drugs used during the treatment.

Cytokine alterations and cognitive impairment in major depressive disorder: From putative mechanisms to novel treatment targets.

Overwhelming evidence indicates the involvement of immune-inflammatory processes in the pathophysiology of major depressive disorder (MDD). Peripheral cytokine alterations serve as one of most consistently reported indices of subthreshold inflammatory state observed in MDD. Although cytokines cannot pass directly through the blood-brain barrier, a number of transport mechanisms have been reported. In addition, peripheral cytokines may impact central nervous system via downstream effectors of their biological activity. Animal model studies have provided evidence that cytokines might impact cognitive performance through direct and indirect effects on long-term potentiation, neurogenesis and synaptic plasticity. Therefore, it has been hypothesized that cytokine alterations might contribute to cognitive impairment that is widely observed in MDD and persists beyond episodes of acute relapse in the majority of patients. Although several studies have provided that peripheral cytokine alterations might be related to cognitive deficits in patients with MDD, the quality of evidence still leaves much to be desired due to methodological heterogeneity and limitations. In this article, we provide an overview of studies investigating the association between peripheral cytokine alterations and cognitive performance in MDD, discuss underlying mechanisms and neural substrates. Finally, we propose possible treatment targets related to cytokine alterations taking into account existing evidence for antidepressant efficacy of anti-inflammatory pharmacological treatment modalities.

Assessment of the frequency criterion for the diagnosis of non-suicidal self-injury disorder in female adolescents with conduct disorder.

Recent studies suggest a higher threshold number of self-injuries during the past year than the one proposed in the DSM-5 criteria for non-suicidal self-injury disorder (NSSID). Therefore, we aimed to test a validity of the frequency criterion in girls with conduct disorder (CD) based on psychopathology and the level of functioning. Mixture modelling analysis revealed that the frequency of at least 8 self-harm behaviours in the previous year differentiated adolescents with CD. Thus, we divided adolescents into three subgroups: group 1: at least 8 self-harm acts; group 2: 1-7 self-harm behaviours and group 3: those who did not injure themselves during the last 12 months. Individuals from group 1 were significantly younger and had earlier age of self-harm onset. There were significant differences between groups 1 and 3 in terms of anxiety and depressive symptoms, self-esteem, aggression and the global functioning level. The group 1 scored significantly higher on depressive symptoms compared to the group 2. The group 2 scored significantly higher than the group 3 on the level of hostility. Our results provide further evidence supporting the need for modification of the NSSID frequency criterion.

[The influence of clomipramine on CYP2D6 activity]. / Wplyw klomipraminy na aktywnosc CYP2D6--doniesienie wstepne.

AIM: Genetically determined activity ofCYP2D6 may be modified by some drugs through inhibition processes. Inhibition properties of TCA's were confirmed mainly in in vitro studies. The aim of the study was to assess the influence of clomipramine on CYP2D6 activity in vivo. METHOD: 11 patients diagnosed with depression according to ICD-10 and DSM-IV (major depression) criteria were included in the study. In all the cases clomipramine therapy was indicated. CYP2D6 activity was assessed by the phenotyping method. All patients were treated simultaneously. Each of the patients ingested one tablet containing 100 mg of sparteine sulfate. Urine excreted during the following 6 h was collected. Based on sparteine metabolic ratio (MR) the phenotype status was estimated twice: after the wash-out period, before clomipramine treatment, sparteine metabolic ratio (MRI), and after 2-weeks of clomipramine treatment (MR2). RESULTS: During clomipramine treatment MR2 values were statistically significantly higher than MRI. In 3 patients (27.3%) treated with clomipramine the changes of phenotype status were observed. CONCLUSIONS: Clomipramine is a CYP2D6 inhibitor and may change the CYP2D6 phenotype status (EM into PM).

Serotonin-Related Gene Variants in Patients with Irritable Bowel Syndrome and Depressive or Anxiety Disorders.

AIM: To assess the association of six polymorphisms in serotonin-related genes with depressive or anxiety disorders in patients with irritable bowel syndrome (IBS). METHODS: The lifetime prevalence of depressive and anxiety disorders was assessed in 95 IBS patients (85% women) using the Munich version of the Composite International Diagnostic Interview (CIDI). IBS was diagnosed according to the Rome III criteria. SCL6A4 HTTLPR polymorphism (rs4795541) was determined using PCR-based method. Single-nucleotide polymorphisms in HTR1A (rs6295), HTR2A (rs6313 and rs6311), HTR2C (rs6318), and TPH1 (rs1800532) were detected by minisequencing method. RESULTS: IBS patients with depressive disorders were characterized by higher frequency of 5-HTTLPR L allele in comparison to IBS patients with anxiety disorders. The lower frequency of 1438 A allele in HTR2A was found in IBS patients with depressive disorders in comparison to IBS patients without mental disorders. The lower G allele frequency in HTR2C rs6318 polymorphism among IBS patients with anxiety disorders was also observed. CONCLUSIONS: Our results provide further evidence for the involvement of SLC6A4 rs4795541 and HTR2A rs6311 polymorphisms in the pathophysiology of depressive disorders in IBS patients. The new findings indicate that HTR2C rs6318 polymorphism may be associated with the susceptibility to anxiety disorders in IBS patients.

[Therapeutic monitoring of tricyclic antidepressant drugs]. / Monitorowana terapia trójpierscieniowymi lekami przeciwdepresyjnymi.

Therapeutic drug monitoring (TDM) is used to optimise therapy by an assessment of the drug's plasma concentration. The indications for TDM according to Preskorn are: 1. well defined relationships between plasma concentration of a drug and its therapeutic efficacy, and between plasma level and adverse events and/or toxicity, 2. narrow therapeutic index of a drug, 3. significant interindividual variability of the dose--plasma concentration relationship, 4. delayed onset of action, 5. difficulty in early diagnosis of toxic events. Tricyclic antidepressants (TCA's) fulfill many criteria for TDM. Interethnic and interindividual differences in pharmacokinetics of TCA's lead to pronounced differences of plasma level. Interindividual variability of plasma concentration of TCA's is connected with age, concomitant diseases, genetically determined polimorphism of cytochrome P-450 enzymes (e.g. CYP2D6) and co-medications (the drug may change pharmacokinetic properties of TCA's). There is no clear relationship between plasma concentration of TCA's and therapeutic efficacy of a drug. Contrary there is clear correlation between plasma level and adverse events (especially cardiotoxic and neurotoxic AE). Therapeutic ranges of plasma concentration for TCA's are well established. In the case of SSRI's or newer antidepressants the clear relationship between plasma level and their therapeutic effect, that is their efficacy and tolerability has not been determined yet. The relationships between plasma concentrations and efficacy and tolerability of TCA's, as well as therapeutic ranges of TCA's and other antidepressants are presented in this paper.

[Assessment of CYP2D6 activity as a form of optimizing antidepressant therapy]. / Badanie aktywnosci CYP2D6 jako forma optymalizacji terapii lekami przeciwdepresyjnymi.

Cytochrome 2D6 catalyzes oxidation processes of many antidepressants (TCAs, SSRIs, maprotyline, mianserine, nefazodon, trazodon, venlafaxine). CYP2D6 is characterized by genetically determined polymorphism which may lead to serious clinical consequences. Based on CYP2D6 activity four phenotypes are distinguished: poor metabolism (PM), intermediate (IM), extensive (normal) EM and ultrarapid (UM). In case of PM and IM increased plasma concentration of a drug and adverse events or toxicity may appear. Decreased plasma level and lack of clinical effect may be connected with the ultrarapid phenotype. CYP2D6 activity may be assessed by phenotyping or genotyping . Model drugs such as sparteine, debrisoquine, dextromethorphan and metoprolol are used in the phenotyping method. Based on the metabolic ratio of model drug the phenotype status is established. Genotyping consists in an assessment of genotype i.e. an identification of alleles coding the CYP2D6 protein. The environmental factors may modify the CYP2D6 activity and have influence on phenotyping but not genotyping results. The knowledge of CYP2D6 phenotype is of special value when drugs characterized by a narrow therapeutic index are used and in polymedicated and older patients.

The lifetime prevalence of anxiety disorders among patients with irritable bowel syndrome.

BACKGROUND: The prevalence of irritable bowel syndrome (IBS), the most common functional gastrointestinal disorder, ranges from 10% to 20% in the general population. It is estimated that from 40% to 90% of persons with a diagnosis of IBS suffer from mental disorders, mainly anxiety and depressive disorders. OBJECTIVES: The aim of the study was to assess the lifetime prevalence of anxiety disorders in IBS patients and to compare it with the prevalence of these disorders in a control group of patients with gastroesophageal reflux disease (GERD). MATERIAL AND METHODS: The study included 106 patients with IBS and 53 patients with GERD. IBS was diagnosed according to the Rome II criteria after a basic evaluation to exclude an organic disease. Anxiety disorders were diagnosed using the Composite International Diagnostic Interview (CIDI) in accordance with ICD-10 diagnostic criteria. RESULTS: Anxiety disorders during the patient's lifetime were diagnosed in 50 IBS patients (47%). Specific phobias occurred in 23.5% of them, social phobias in 10.4%, generalized anxiety disorder in 10.4%, panic disorder in 3.8% and agoraphobia in 8.5%. In the control group with GERD, anxiety disorders during the subject's lifetime were diagnosed in 30% of the group. The difference in the prevalence of anxiety disorders between patients with IBS and GERD was statistically significant (p<0.05). CONCLUSIONS: The lifetime prevalence of anxiety disorders in IBS patients was higher than in the control group with GERD (47% vs. 30%). The prevalence rate of anxiety disorders in the control group with GERD was similar to the prevalence rate in the general population.

Doxepin inhibits CYP2D6 activity in vivo.

OBJECTIVE: Doxepin is a tricyclic antidepressant formulated as a mixture of E-(trans) and Z-(cis) stereoisomers. Cytochrome P450 2D6 (CYP2D6) catalyzes the hydroxylation of E-doxepin and E-N-desmethyldoxepin stereospecically. There is evidence that tricyclic antidepressants might inhibit CYP2D6 activity but there is no data about the influence of doxepin on CYP2D6. MATERIALS AND METHODS: Eleven patients diagnosed with depression according to ICD-10 criteria were included in the study. After wash-out period, before doxepin treatment, sparteine metabolic ratio (MR1) was assessed. After 2-weeks of doxepin treatment, MR2 was estimated. Sparteine and its metabolites were determined in urine by gas chromatographic method of Eichelbaum et al. RESULTS: Based on MR1 values, 10 patients were classified as EM (extensive metabolizers) and 1 patient as PM (poor metabolizer). During the study, after doxepin treatment, none of patients has changed phenotype status. However, MR2 values were statistically significantly higher than MR1. CONCLUSION: These results show the inhibitory effect of doxepin on CYP2D6 activity and may be of clinical value, especially in polymedicated patients treated with other CYP2D6 substrates or inhibitors.