Türkiye Sinir ve Ruh Sağlığı DerneğiTurk Psikiyatri Derg1300-21633322022SummerEditorial: Telepsychiatry Throughout and Thereafter The PandemicA3A4TRHakanKARAŞİlkerKÜÇÜKPARLAK129110.5080/u27177

Türkiye Sinir ve Ruh Sağlığı DerneğiTurk Psikiyatri Derg1300-21633322022SummerEvaluation of Resting-State Functional Magnetic Resonance Imaging Findings of Patients with Social Anxiety DisorderSosyal Anksiyete Bozukluğu Olan Hastalarda Dinlenim Durumu İşlevsel Manyetik Rezonans Görüntüleme Bulgularının İncelenmesi738110.5080/u25991ENTRCeylanERGÜLÇiğdem ULAŞOĞLUYILDIZElifKURTAniKIÇİKRaşitTÜKEL129210.5080/u25991Objective: The most prominent functional magnetic resonance imaging findings about social anxiety disorder are increased activity in emotional regulation areas (amygdala, insula, hippocampus, dorsal anterior cingulate cortex) and fear circuit, and altered activity in prefrontal cortex. This study aims to investigate network abnormalities during resting state. Method: Resting state functional magnetic resonance images of 21 drug-free patients with social anxiety disorder and 21 healthy controls (matched on age, gender, and years of education) were recorded. Resting state functional connectivity networks were obtained with independent component analysis, and were compared by using the voxel based t-test between the two groups. Results: Patients with social anxiety disorder displayed decreased intrinsic functional connectivity in the anterior component of the salience network (left orbitofrontal cortex) and increased intrinsic functional connectivity in the posterior component of the salience network (left supramarginal gyrus). Conclusion: Most of the studies about social anxiety disorder mainly focused on fear circuit and emotional regulation areas by using anxiety provoking tasks or by using seed based analysis of functional connectivity. By applying a whole-brain independent component analysis, we found altered functional connectivity in the salience network, but no significant difference was found in the fear circuit areas. Our results suggest that abnormal connectivity in the salience network might play a crucial role in the neurobiology of social anxiety disorder. Keywords: Social Anxiety Disorder, Functional Magnetic Resonance Imaging, Salience Network, Orbitofrontal Cortex, Supramarginal Gyrus

Türkiye Sinir ve Ruh Sağlığı DerneğiTurk Psikiyatri Derg1300-21633322022SummerInvestigation of the Metacognitive Model of Depression in a Turkish Sample of Major DepressiveDepresyonun Üstbilişsel Modelinin Türkiye’deki Bir Majör Depresif Bozukluk Örneklemi Üzerinde İncelenmesi828910.5080/u26082ENTRAdviye EsinYILMAZGülizŞENORMANCIÖmerŞENORMANCI129310.5080/u26082Objective: The aim of this study was to test the metacognitive model of depression in individuals diagnosed with major depressive disorder (MDD) and to investigate the relative contributions of cognitions and metacognitions about rumination to the explanation of depressive symptoms. Method: The participants of the study consisted of 180 MDD patients not meeting the diagnostic criteria for other psychiatric disorders. The obtained data were analyzed through structural equation modelling (SEM) and hierarchical regression analyses. Results: SEM results showed that positive beliefs about rumination increased the rumination level, and the higher levels of rumination significantly predicted the increase in depressive symptoms partly through the mediating effect of negative metacognitive beliefs about rumination regarding interpersonal and social consequences. However, negative metacognitive beliefs about the uncontrollability and danger of rumination were not found to be associated with symptoms of depression in the participants of this study. The power of dysfunctional attitudes for predicting depression was lost when hierarchical regression analysis was carried out by controlling the metacognitions about negative interpersonal and social consequences of rumination. Conclusion: The results are consistent with the metacognitive model of depression, which was originally developed for better understanding of MDD, and point to the usefulness of considering positive and negative metacognitions about rumination in the processes of clinical evaluation and intervention for MDD. Keywords: Major depressive disorder, depression, rumination, metacognition, metacognitive theory, cognition, cognitive behavioral theory, dysfunctional attitudes

Türkiye Sinir ve Ruh Sağlığı DerneğiTurk Psikiyatri Derg1300-21633322022SummerRelationship Between Sleep Disorders and Attention Deficit- Hyperactivity Disorder Symptoms in University StudentsÜniversite Öğrencilerinde Uyku Bozukluğu ile Dikkat Eksikliği Hiperaktivite Bozukluğu Belirtileri Arasındaki İlişki909610.5080/u25503ENTRElçin ÖZÇELİKEROĞLUDemet SAĞLAMAYKUTSevilayKARAHANBaşaranDEMİR129410.5080/u25503Objective: Sleep disorders increase the symptoms of attention deficit hyperactivity disorder (ADHD). The aim of this study was to investigate whether or not sleep related problems give rise to symptoms of attention deficit and hyperactivity-impulsivity in university students. Methods: The 252 university students between the ages of 18-25 years included in the study were assessed on the Pittsburgh Sleep Quality Index (PSQI), the Adult Attention-Deficit Hyperactivity Disorder Scale, the Beck Depression Inventory (BDI) and the Beck Anxiety Inventory (BAI). Results: The participants of the study comprised 38.5% males and 61.5% females with a mean age of 22.39 (±1.93) years. The mean score data were 5.78 (± 2.72) on the PSQI, 41.77 (± 20.38) on the Adult Attention-Deficit Hyperactivity Disorder Scale, 8.53 (± 6.97) on the BDI and 9.05 (± 7.92) on the BAI. The total score and the scores on the attention-deficit and the general problems subsections of the Adult Attention-Deficit Hyperactivity Disorder Scale were significantly higher in participants with poor sleep quality (P<0.001). The PSQI and the Adult Attention-Deficit Hyperactivity Disorder Scale scores were significantly above the cut-off values in the participants with depression and anxiety symptoms as compared to those without these symptoms (P<0.001). The PSQI total score positively correlated with the Adult Attention-Deficit Hyperactivity Disorder Scale total score (P<0.001). Conclusion: University students with sleep disorder have more ADHD symptoms and poor quality of sleep increase ADHD sypmtoms. Therefore it’s important to evaluate quality of sleep in young people suffering from attention problems in terms of treatment approaches and interventions. Keywords: Attention deficit-hyperactivity disorder, sleep disorder, sleep quality

Türkiye Sinir ve Ruh Sağlığı DerneğiTurk Psikiyatri Derg1300-21633322022SummerThe Validity and Reliability Study of the Turkish Version of Client Attachment to Therapist Scale (CATS)Danışanın Terapiste Bağlanma Ölçeği (DTBÖ) Türkçe Formu’nun Geçerlik ve Güvenirlik Çalışması9710710.5080/u25582ENTRYaseminKAHYANuray MUSTAFAOĞLUÇİÇEKF. MahperiULUYOLHüseyinNERGİZSaitULUÇGonca SOYGÜTPEKAK129510.5080/u25582Objective: This study aimed to evaluate the validity and reliability of the Turkish version of Client Attachment to Therapist Scale (CATSTR) which provides a framework for measuring and conceptualizing the relationship between the therapist and the client. Method: The study included 191 individuals with a mean age of 24.41 years who had received a minimum of 5 and a maximum of 15 sessions of therapy for different psychological problems. All participants completed the CATS-TR, the Early Close Relationships-R (ECR-R), the Bell Object Relations Inventory (BORRTI), and the Working Alliance Inventory (WAI-SF), and a Client Information Form handed to the clients in a closed envelope by their respective therapists. Results: Exploratory and Confirmatory Factor Analysis results indicated an acceptable fit for the CATS-TR which comprised the Secure, Fearful/Avoidant and Preoccupied/Merger subscales, with internal consistency levels ranging between 0.71 and 0.85. Criterion validity analyses showed that the scores on the CATS-TR Fearful/Avoidant and Preoccupied/Merger subscales correlated with the scores on the ECR-R Avoidance/Anxiety subdimesnions and the BORRTI Object Relations subdimension in the expected directions. Also, the mean score on the CATS-TR Secure Attachment subscale was a significant predictor of the therapeutic alliance assessed by the WAI-SF and its subscales. Conclusion: This study has demonstrated that the CATS-TR has an acceptable level of validity and reliability with results indicating its usefulness for research and clinical settings in Turkey investigating the common factors bringing about change in psychotherapy. Keywords: Attachment to therapist, therapeutic alliance, measuring attachment in psychotherapy

Türkiye Sinir ve Ruh Sağlığı DerneğiTurk Psikiyatri Derg1300-21633322022SummerReliability and Validity of the Turkish Version of SF-12 Health SurveySF-12 Yaşam Kalitesi Ölçeği’nin Türkçe Formunun Güvenirlik ve Geçerlik Çalışması10811710.5080/u25700ENTRCemSOYLUBahtımKÜTÜK129610.5080/u25700Objective: The aim of this study is to determine the psychometric properties of the Turkish version of the SF-12 Health - a widely used scale that assesses health - related quality of life - and to assess whether its psychometric properties are as good as with the 36 items long version (SF-36). Method: The study included a total of 190 participants including 138 young adults aged from 18 to 29 years (22.04±2.35) and 52 older adults aged from 60 to 80 years (67.27±5.22). The relationships between EQ-5D-3L, CES-D and SF-12 scales were investigated for content, convergent and divergent, criterion-related and the known-groups construct validity. In order to assess reliability, internal consistency and item-total correlation coefficients were calculated and test re-test analyses were conducted. Results: The internal consistency coefficients of the scale were found to be satisfactory (for the components α=0.73 and 0.72). Consistent with the original study, physical and mental components of the SF-12-TR were found to be strongly correlated with the components of the SF- 36 and explained, respectively, 86.6% and 92.4% of the variance. The components of the SF-12-TR were found to be moderately or strongly correlated to the sub-dimensions of the EQ-5D-3L and CES-D, which measure the same structures, while they were unrelated or weakly correlated with the sub-dimensions measuring different structures. Conclusion: The findings indicated that the psychometric properties of the Turkish form of SF-12-TR are similar to the original version, and the SF-12-TR can be used as an alternative to the SF-36-TR in clinical and research settings in our country. Keywords: The SF-12-TR, reliability, validity, the SF-36-TR

Türkiye Sinir ve Ruh Sağlığı DerneğiTurk Psikiyatri Derg1300-21633322022SummerPrevalence of Personality Disorder Diagnosed with SCID-II Among Psychiatry Patients in Turkey: Systematic Review and Meta-AnalysisTürkiye’de Psikiyatri Hastalarında SCID-II ile Tanılanan Kişilik Bozukluğunun Prevalansı: Sistematik Gözden Geçirme ve Metaanaliz11813210.5080/u26104ENTRFerhanDEREBOYÇiğdemDEREBOYServet KAÇARBAŞARANÇiğdem KIRCIDALLIOĞLUDuygu ASLANKUNT129710.5080/u26104Objective: To review and summarize data on the prevalence of overall personality disorder extracted from SCID-II (Structured Clinical Interview for DSM-III Axis II Disorders) studies conducted in Turkey with samples consisting of mental health consumers, and also to elaborate on the level and sources of heterogeneity. Method: MEDLINE, WOS, PsycINFO, ScienceDirect databases as well as the Turkish Psychiatric Database have been systematically searched. Relevant studies conducted with samples composed of psychiatric inpatients or outpatients receiving psychiatric treatment were included. The diagnostic rate of any personality disorder was regarded as the valid indicator of the overall personality disorder prevalence; therefore, papers presenting data not conducive to this goal were excluded. Results: A total of 311 papers were identified, and 55 studies were included in the qualitative synthesis. Following a critical appraisal of the quality of the data involving point prevalence rates ranging from 20% to 100%, we decided to include 35 studies in the quantitative synthesis. A random-effects meta-analysis followed by a subgroup analysis yielded a summary estimate of 52% [46 – 58%] for the prevalence of overall personality disorder. A high level of overall heterogeneity 84.8 % [80.0 - 88.4] was found to persist in each diagnostic subgroup with a particular primary diagnosis. Conclusion: The prevalence estimates derived from the meta-analysis of the SCID-II studies conducted in Turkey support the notion that personality disorder is present in nearly half of the mental health service consumers. That the level of heterogeneity across studies originating from Turkey alone was as high as those observed in previous reviews covering studies originating from various countries suggests that the very source of such heterogeneity might be questionable validity and reliability of SCID-II diagnoses. Keywords: Personality disorders, prevalence, meta-analysis

Türkiye Sinir ve Ruh Sağlığı DerneğiTurk Psikiyatri Derg1300-21633322022SummerFunctional Movement Disorder and Parkinson’s Disease Comorbidity: A Case ReportFonksiyonel Hareket Bozukluğu ve Parkinson Hastalığı Eş Tanısı: Bir Olgu Sunumu13313810.5080/u25740ENTRSelmaERTÜRKVildan ÇAKIRKARDEŞÖzgeSARAÇLIEsra ACIMANDEMİREL129810.5080/u25740Functional movement disorders (FMD) are abnormal involuntary movements that are not attributable to known neurological and neuroanatomical causes. In the past decade, FMD diagnoses have been based on positive factors that are inconsistent with neurological disorders and not on the exclusion of neurological disorders. In this report, we presented the case of a female patient who had been followed up for 4 years in multiple health centers with the diagnosis of a neurological disorder which was suspected in the previous 1 year to be of psychogenic origin. A neurological disorder comorbid with depression and FMD was diagnosed after admission as an inpatient to our clinic. By presenting this case, it was intended to emphasise the importance of follow up after diagnosing FMD, given its common basis with Parkinson’s disease and the high incidence of comorbidites seen with it. Imaging and elecrophysiological techniques should be relied upon.for differentiating FMD and neurological diseases. Although psychological causes are significant disease risk and/or maintenance factors, they are not sufficient for explaining the aetiology of FMD, which requires a multidisciplinary approach. Keywords: Functional movement disorders, Parkinson’s disease, DaTscan

Türkiye Sinir ve Ruh Sağlığı DerneğiTurk Psikiyatri Derg1300-21633322022SummerA Severe Neuroleptic Malignant Syndrome Treated with Daily Electroconvulsive Therapy: A Case ReportGünlük Elektrokonvülzif Terapi ile Tedavi Edilen Şiddetli Nöroleptik Malign Sendrom: Bir Olgu Sunumu13914210.5080/u26535ENTRÖzlem ERDENAKİAhmetGÜRCANŞ. CanGÜRELM. KâzımYAZICI129910.5080/u26535Neuroleptic malignant syndrome (NMS) is a rare but life-threatening condition caused by dopamine modulating medications, particularly antipsychotics. First-line treatments of neuroleptic malignant syndrome are supportive care, discontinuation of the offending agent and pharmacotherapy. In drug-resistant and severe situations, electroconvulsive therapy (ECT) is recommended as well. In this paper we present a 23-year old male with bipolar disorder who was treated with multiple injections of zuclopenthixol long acting and depot forms for a recent manic episode and developed NMS. The patient was transferred to an intensive care unit, medical management was initiated including benzodiazepines, bromocriptine and dantrolene. Due to the inadequate response after several days, ECT (bitemporal electrode placement, briefpulse, on a daily basis) was initiated. After 17 sessions, NMS relieved and there was no need for maintenance ECT. The patient is under follow-up care for 3 years with no cognitive and physical sequela. Keywords: Electroconvulsive therapy, neuroleptic malignant syndrome, bipolar disorder

Türkiye Sinir ve Ruh Sağlığı DerneğiTurk Psikiyatri Derg1300-21633322022SummerLetter to the Editor: Depression As The First Symptom Of Frontal Lobe Grade 2 Malignant GliomaEditöre Mektup: Frontal Lob Yerleşimli Derece 2 Malign Glioma Olgusunda İlk İşaret Olarak Depresyon14314510.5080/u25957ENTRŞerif BoraNazlıMuhammetSevindik130010.5080/u25957Dear Editor, Next to focal neurological symptoms, epileptic seizures and head aches, brain tumors can less frequently bring about cognitive changes, slowed speech, difficulty sustaining mental functioning and psychiatric symptoms of personality changes and. loss of interest in daily activities, these symptoms may be evaluated as anxiety or depression. Depression is known to be a complication of brain tumours and may sometimes be seen after the presentation of neurological symptoms linked to brain tumours, and sometimes after tumor treatment (Oğuz et al. 2005, Litofsky et al. 2004, Moise and Madhusoodanan 2006, Oreskovic M et al. 2007, Rooney A et al. 2010). The dorsolateral prefrontal, orbitofrontal and medial frontal circuits constitute the three subcortical neuronal circuits in the frontal cortex. The dorsolateral prefrontal circuit is associated with planning and operational functions and lesions on it may give rise to apathy, abulia, perseveration, personality changes and planning disorder. Lesions involving the orbitofrontal circuit, which is associated with response suppression and disinhibition, may involve emotional lability and memory problems. Whereas lesions affecting the right orbitofrontal circuit give rise to elevated mood, lesions on the left orbitofrontal circuit lead to depressed mood. In cases with medial frontal circuit involvement, akinetic mutism may result from lesions in the superior medial region and anteroretrograde amnesia and confabulation are observed with lesions in the inferior medial region (Tosun et al. 2016, Chirchiglia 2018). A diagnosis of psychiatric disorder may be given during the first examination of patieants with primary brain tumours, especially if localized in the frontal lobe. Thorough history taking and physical examination are necessary for early diagnosis. The case reported here concerns a 29-year-old university graduate female patient, living with her partner and children, who consulted the clinic with complaints of tendency to frequent crying, anhedonia, having difficulty with speech fluency, forgetfulness and distractedness that had presented suddenly, 2 months previously, without any causative stressor. In her mental status examination, she appeared having normal self-care with appearance at her actual age. She was fully conscious and oriented, not willing to cooperate with the interview, had distinct difficulty in maintaining attention and with fluency of speech. Her mood was depressive. She described loss of appetite, fatigue and energy loss. Her difficulty in paying attention was pronounced. She did not have a history of psychotropic medication use or family history of psychiatric disease. She did not smoke or use alcohol or substance. After evaluating the clinical interview, a preliminary diagnosis of major depressive disorder was considered on the basis of the DSM-5 criteria. Routine blood tests were requested. Given the continuation of her complaints, the difficulty with fluent speech and the increase in tendency to sleep at the first week follow up, cranial MRI was planned. The MRI results showed on the right, in the frontal lobe a multilocular mass with precallosal extension, undiscernable margins with the right lateral aspect of the corpus callosum genu and dispersed cystic-necrotic areas with T2 signal series. The dimensions of the mass were nearly 5 x 3 cm causing a 1-cm right-to-left shift of the midline (Figure 1) DEPRESSION AS THE FIRST SYMPTOM OF FRONTAL LOBE GRADE 2 MALIGNANT GLIOMA 2 Türk Psikiyatri Dergisi 2 Turkish Journal of Psychiatry Letter to the Editor 143 144 The patient was referred for surgery with the preliminary diagnosis of high-grade glial tumour. Pathology results identified a grade 2 glioma. It was learned that radiotherapy sessions were begun after surgery. The patient did not have any symptoms of psychopathology during the 2 monthly psychiatric interviews made after surgery. Brain tumours generally indicate their presence with headache, seizures and other neurological symptoms and very rarely with depression as seen in the case of our patient. It should be kept in mind that atypical psychiatric symptoms may have an underlying organic lesion and subtle neurological symptoms should be investigated in detail. A recent meta-analysis on 37 observational studies determined a 21.7% prevalence of depression in a total of 4518 patients with intracranial tumours. Comorbidity of depression with brain tumor was demonstrated to worsen the quality of life, increase suicidal risk and lower the chance of survival (Huang et al. 2017). The possibility of psychiatric symptoms being the clinical clues for brain cancer was noted and the necessity of neuroimaging tests in cases of recent-onset psychosis or mood disorder symptoms, atypical personality changes and anorexia without body dysmorphic disorder was emphasized (Madhusoodanan et al. 2015). Loss of interest, tendency to frequent weeping, introversion and anhedonia were the sole complaints in the case discussed here. The increase in psychomotor retardation and slowing down of movements at the very first weekly control follow up necessitated neuroimaging. Despite the reports in the literature on the frequent association of unpreventable excessive behavior, disinhibition and irritability with right frontal injury and lesions (Okumuş and Hocaoğlu 2018), depression was the dominant symptom in the case presented here. There are differences between primary major depression and depression presenting with underlying somatic diseases which is known to occur at later ages (Rouchell et al. 2002). However, our patient was aged 29 years. Also, cases of depression due to somatic disease are less associated with family history of depression and suicidal ideation and attempts, while cognitive symptoms come to the foreground during mental status examination. (Sertöz and Mete 2004, Rouchell et al. 2002). Our patient did not have suicidal ideation or attempts, or a family history of depression. In apathy, which may be explained as emotional blunting, indifference or detachment from the external world, targeted behavior is also reduced next to the lack of emotional expression. The individual discussed here was learned not to sit at the table or change the television channel unless reminded to do so. When the reason was asked, she could not think of one. The reduction in emotional expression accompanies reduced insight, abulia and lack of empathy (Sözeri Varma et al. 2019). In depression, apathy is defined as ‘sorrowless depression’. Our patient cried but had very blunted mimics and gestures. She explained that she could not help weeping even at times when she did not feel internally distressed. The seriousness of apathy, as a symptom difficult to differentiate from depression, is still not understood. Neuroimaging Figure 1- Cranial MRI of the patient 145 Received: 16.08.2020, Accepted: 04.12.2020, Available Online Date: 05.10.2021 1MD., Antalya Kepez State Hospital, Department of Psychiatry, Antalya, 2MD., Ordu University Training and Research Hospital, Department of Psychiatry, Ordu, Turkey e-mail: bosbora@yahoo.com https://doi.org/10.5080/u25957 studies indicate apathy to be a reflect of impaired frontal-subcortical circuits and the functional disorder of the connections between the ventromedial prefrontal cortex and the basal ganglia (Chase 2011). Comparison of 45 individuals with depression due to aging and 43 healthy individuals showed apathy to be associated with fronto-limbic gray and white matter abnormalities which continued after antidepressant treatment. The structural anomalies of the posterior subgenual cingulate gyrus and the uncinate fasciculus were discussed (Yuen 2014). The case discussed here is presented to emphasize the importance of brain imaging methods and detailed investigation of atypical symptoms for diagnostic approaches to psychiatric disorders. Especially, complaints at young age of depression with psychomotor retardation, reduced fluency of speech and sudden onset withdrawal without stressors should be a warning of secondary depression. Yours sincerely... Şerif Bora Nazlı1 , Muhammet Sevindik2 REFERENCES Chase TN (2011) Apathy in Neuropsychiatric Disease: Diagnosis, Pathophysiology, and Treatment. Neurotox Res 19:266–78. Chirchiglia D (2018) Pseudodepression as an Anticipatory Symptom of Frontal Lobe Brain Tumors. Int J Depress Anxiety 1:007. Huang J, Zeng C, Xiao J et al (2017) Association between depression and brain tumor: a systematic review and meta-analysis. Oncotarget 8:94932-43. Litofsky NS, Farace E, Anderson F et al (2004) Depression in patients with high-grade glioma: Results of the glioma outcomes project. Neurosurgery 54:358-67. Madhusoodanan S, Ting MB, Farah T et al (2015) Pyschiatric aspects of brain tumors: A review. World J Psychiatry 5:273-85. Moise D, Madhusoodanan S (2006) Psychiatric symptoms associated with brain tumors: a clinical enigma. CNS Spectr 2006;11:28-31. Oğuz N, Ilnem C, Yener F (2005) Psychiatric symptoms in brain tumors: Case reports. Bulletin of Clinical Psychopharmacology 15:18-21. Hocaoğlu Ç, Okumuş B (2018) Psychiatric manifestations and brain tumor: A case report and brief review. The Medical Journal of Mustafa Kemal University 9:42–9. Oreskovic NM, Strother CG, Zibners LM (2007) An unusual case of a central nervous system tumor presenting as a chief complaint of depression. Pediatric Emergency Care 23:486-8. Rooney A, Carson A, Grant R (2011) Depression in cerebral glioma patients: a systematic review of observational studies. J Natl Cancer Inst103:61–76. Rouchell AM, Pounds R, Tierney JG (2002) Depression Textbook of Consultation-Liaison Psychiatry, 2nd Edition, Volume 1. MG Wise, JR Rundell (Ed), Washington DC American Psychiatric Publishing, Inc, p.307-38. Özen SÖ, Hayriye ME (2004) Bedensel Hastalıklarda Depresyon. Klinik Psikiyatri Ek 2:63-9. Sözeri Varma G , Bingöl C , Topak O et al (2019) Relationship of apathy with depressive symptom severity and cognitive functions in geriatric depression. Arch Neuropsychiatry 56:133−8. Yuen GS, Gunning FM, Woods E et al (2014) Neuroanatomical correlates of apathy in late-life depression and antidepressant treatment response. J Affect Disord 166:179–86.

Türkiye Sinir ve Ruh Sağlığı DerneğiTurk Psikiyatri Derg1300-21633322022SummerLetter to the Editor: Rethinking The Cost Of Antipsychotic Treatment: The Average Cost Of The Drugs Used In Turkey In 2020Editöre Mektup: Çıldırıgideren İlaç Tedavisinde Maliyeti Yeniden Düşünmek: Türkiye’de Kullanılan İlaçların 2020 Yılı Ortalama Tedavi Maliyeti14614810.5080/u26315ENTRMustafaYıldızEmreOsman130110.5080/u26315Dear Editor, The costs of antipsychotic drugs (APDs) used in the treatment of mental disorders with psychosis are mentioned in treatment guidelines (APA 2021, NICE 2014). While the American Psychiatric Association guideline states that every specialist should make decisions according to the rules and conditions of their country and their region, the National Institute of Health and Clinical Excellence guideline emphasizes that drug costs must be taken into consideration in the treatment process. Classical or first-generation antipsychotic drugs (FAPDs) are relatively cheaper in terms of sales prices compared to atypical or second-generation antipsychotic drugs (SAPDs) with a slightly different effect mechanism. The price difference between the two drug groups can be so large that sometimes it may be necessary to consider whether the cost of a second-generation drug is worth its benefit. While deciding on the use of first-generation or second-generation drugs, a multifaceted assessment should be made, such as the patient’s level of compliance with the treatment, the possibility of occurrence of side effects, the possible effects of these side effects on body health and treatment compliance, and whether or not the costs are covered. The most important criterion that determines the choice of medication for psychiatrists is of course the multi-dimensional benefit/harm ratio that the drug used will reveal in the long term. We think that in our country, which, in terms of economic indicators is not in a strong position as an importer of pharmaceutical raw materials from abroad, APDs’ cost calculation should be considered because drug costs constitute an important part of the direct treatment costs of psychotic disorders in developing countries such as Turkey (Yıldız and Cerit 2006). We calculated the unit (mg) price based on the box prices of the APDs in use in 2020, thinking that it might work when calculating the cost of the illness using APDs as the main component of the treatment and calculated the annual average drug costs with the daily average dosage. Although the daily treatment dose varies with the stage of the illness and the individual characteristics of the patient, the average doses recommended for maintenance treatment were used here (Öztürk and Ulusahin 2018). The daily and annual cost calculations based on the assumption that the average maintenance treatment dose was used with the unit price obtained from (Drug Prices 2020) the drugs in the Turkish pharmaceutical market in September 2020 are shown in Table 1. A similar study was done in 2005 (Yıldız 2005). The purpose of this article is to redetermine the average costs of APDs in the Turkish pharmaceutical market every 15 years and to bring them to the attention of experts in terms of cost-effectiveness studies. When the costs in 2005 are examined, it is seen that the annual costs of the FAPDs were around 450 TRY, and the annual cost of oral preparations of SAPDs was 2,500 TRY (5 times the first generation). In 2005, there was only one depot of SAPD (risperidon consta) that allowed intramuscular (IM) administration, and its average annual cost was 5,400 TRY, 3 times more than the tablet form (1,700 TRY). In 2005, when the price of risperidone consta, which was the first second-generation depot APD, were compared with the prices of the first-generation depot drugs (fluphenazine = 380 TRY, flupentixol = 876 TRY, zuclopentixol = 730 TRY), the cost difference was 6-14 times. This almost-10-fold difference between the cost of the first and second generation APDs was remarkable. It is seen that this difference (risperidone consta = 10,807 TRY, fluphenazine = 916 TRY, flupentixol = 1,007 TRY, zuclopenthixol = 2,372 TRY, and haloperidol deconate 237 TRY) did not change in 2020. In 2020, the average RETHINKING THE COST OF ANTIPSYCHOTIC TREATMENT: THE AVERAGE COST OF THE DRUGS USED IN TURKEY IN 2020 2 Türk Psikiyatri Dergisi 2 Turkish Journal of Psychiatry Letter to the Editor 146 147 annual cost of oral use preparations of FAPDs is 925 TRY, while the average annual cost of oral forms of SAPDs is 2,580 TRY. The 5-fold difference observed in 2005 between the first and second-generation ones of the oral APDs decreased to 2.5 times in 2020. It is clear that while the difference between the cost of oral use of first- and second-generation drugs was halved in 2020, the difference between the costs of depot preparations applied with IM did not change. In 2005, the average dollar rate was 1.34 TRY, and in 2020 it was 7.02 TRY (Republic of Turkey Central Bank Exchange Rates, 2021). It is understood that the 5-fold increase in dollar exchange rate is not reflected in all drug prices in the same way. For example, there was a 3 to 4-fold increase in the prices of haloperidol, chlorpromazine, fluphenazine, trifluperazine and zuclopenthixol, while a less than two-fold increase in pimozide, flupenthixol, sulpiride, amisulpride and quetiapine and a decrease in the prices of clozapine, olanzapine, ziprasidone and risperidone in the tablet form. There is also a two-fold increase in the price of risperidone consta. The fluctuations in drug prices in 2005 and 2020 are shown in Table 2 in 500, 1,000, 2,000, 3,000 and 5,000 TRY brackets. It is noteworthy that while some drugs have moved into an upper price bracket in terms of annual costs, some have fallen into a lower price bracket. The prices of the second generation long-acting (depot) antipsycotic drugs (LA-APDs), which were not available in the Turkish pharmaceutical market in 2005, are quite high compared to others. In 2020, the annual cost of all of them, including risperidone consta, is over 10 thousand TRY. It is understood that the underlying reason for such price increase is the fact that the drug is wanted/sought after/new/marketed rather than the dollar exchange rate. For example, while there was a certain increase in the price of FAPDs, the increase in the price of some of the SAPDs (sulpiride, amisulpride, quetiapine tablet) was low, while the price of some others (clozapine, olanzapine, ziprasidone, risperidone tablet) decreased. It should also be taken into account that the effect of generic drugs entering the market during this period may have had an impact on price changes. It is noteworthy that while the annual cost of risperidone consta was approximately 3 times higher than the tablet form (5,400 TRY versus 1,700 TRY) in 2005, this difference reached 14 folds (10,807 TRY versus 742 TRY) in 2020. In 2005, the difference between the lowest daily cost (0.07 TRY) and the highest daily cost (14.80 TRY) was 211 times (Yıldız 2005), this difference had receded to 111 times (0.35 TRY versus 38.72 TRY) in 2020. Still a huge difference, isn’t it? Table 1. Current Forms, Box Prices, Daily and Annual Costs in For Maintenance Treatment of Antipsychotic Drugs Available in the Pharmaceutical Market in September 2020 in Turkey No Generic name Trade name Dosage forms (mg) BV Price# TRY/Mg ADD Cost/d Cost/y 2005** 1 Haloperidol Norodol 5, 10, 20 tb 5/50 17.57 0.070 5 0.35 127 26 5, 10 amp 5/5 5.35 0.214 5 1.07 390 - 50, 150 LAI 50/1 9.80 0.196 1/15* 0.65 237 - 2 Chlorpromazine Largactil 25,100 tb 100/30 17.92 0.006 300 1.79 653 197 3 Fluphenazine Prolixin 25 LAI 25/1 17.57 0.703 1/7* 2.51 916 380 4 Trifluoperazine Stilizan 1, 2, 5 drj; 1 amp 5/30 14.52 0.096 10 0.97 354 91 5 Pimozide Nörofren 2 tb 2/30 19.33 0.322 4 1.29 470 365 6 Flupenthixol Fluanxol 3 drj 3/50 65.75 0.438 6 2.63 960 526 20 LAI 20/1 19.33 0.966 1/7* 2.76 1,007 876 7 Zuklopenthixol Clopixol 2, 10, 25 tb 2/50 38.65 0.386 20 7.72 2,817 701 200 LAI, 50 acu 200/1 45.55 0.227 1/7* 6.50 2,372 730 8 Sulpirid Dogmatil 200 tb 200/24 23.15 0.005 600 3.00 1,095 876 9 Amisulpirid Solian 200 tb 200/60 146.92 0.012 600 7.20 2,628 2,387 10 Quetiapine Seroquel 25, 50, 100, 200, 300, 400 tb 300/30 137.17 0.015 600 9.00 3,285 2,628 11 Clozapine Leponex 25, 100 tb 100/50 32.56 0.006 400 2.40 876 1,898 12 Olanzapine Zyprexa 5, 10, 20 tb 10/28 152.96 0.546 10 5.46 1,992 2,606 13 Ziprasidone Zeldox 20, 40, 60, 80 tb 60/56 189.89 0.056 120 6.72 2,452 3,541 14 Sertindole Serdolect 4, 12, 16, 20 tb 16/28 453.53 1.012 16 16.19 5,909 - 15 Risperidone Risperdal 1, 2, 3, 4 tb; 1 sol 2/20 20.34 0.508 4 2.03 741 1,719 Ris. Consta 25, 37.5, 50 LAI 37.5/1 444.17 11.840 1/15* 29.61 10,807 5,402 16 Paliperidone Invega 3, 6, 9 tb 6/28 213.15 1.268 6 7.61 2,777 - Xeplion 50, 75, 100, 150 LAI 100/1 1161.56 11.615 1/30* 38.72 14,132 - Trevicta 175, 263, 350, 525 LAI 350/1 3426.95 9.788 1/90* 38.08 13,899 - 17 Aripiprazole Abilify 5, 10, 15, 20 tb; 1 sol 20/28 113.25 0.404 20 8.08 2,949 - Abilify Main. 400 LAI 400/1 971.17 2.420 1/30* 32.37 11,815 - BV: Baseline value (in mg of the form and the number in the box), Price#: Box price of the base value in TRY, TRY/mg: Value per milligram in Turkish Lira, ADD: Average daily dose, Cost/d: Daily cost in TRY, Cost/y: Annual cost in TRY, mg: Milligram, tb: Tablet, drj: Dragee, amp: Ampoule, LAI: Long-acting injectable, acu: Acuphase, d: Day, TRY: Turkish Lira, *LAI per 7,15,30 or 90 days, **Annual cost in TRY in 2005. 148 Received: 14.01.2021, Accepted: 31.03.2021, Available Online Date: 07.01.2022 1Prof., 2Res. Assis., Kocaeli University School of Medicine, Department of Psychiatry, Kocaeli, Turkey. e-mail: myildiz60@yahoo.com https://doi.org/10.5080/u26315 The difference in 2005 between oral FAPDs prices and SAPDs prices seems to have halved in 2020. In 2020, the average daily treatment cost of oral drugs, whether for the first generation or the second generation, is 3 TRY (approximately the same for FAPDs applied with IM), while the daily cost of LA-SAPDs is around 33 TRY. It is seen that the difference between costs is approximately 11 times. This difference increases to 50 times for haloperidol deconate. From here, the following judgment can be made: in order for LA-SAPDs to be preferred, they must be at a value that will constitute at least 11 times higher cost. This cost can and should be taken, especially for patients who are non-adherend with treatment and who do not adapt to LA-FAPDs. Because for clinicians, preventing the multi-dimensional destructiveness of psychosis in the individual, families and the society should be the priority. In this case, calculating the cost should not be a primary consideration. However, it is also known that patients who are non-adherend with treatment gain the ability to understand their illness and make consistent evaluations with its’ results. If a psychosocial therapy has been carried out for a patient using IM medication for six months or a year, it is likely that this period provides insight and increases the level of treatment compliance. After one year of IM application, whether or not the patient will comply with oral treatment should be re-evaluated and the transition to oral treatment should be considered. If there is no problem in the patient’s oral treatment compliance, it should be taken into account that the benefit of this transition will be at least 11-folds a year with this transition. Naturally, it will be necessary to apply IM for some patients for years. Moreover, there will be patients who need to switch from monthly administration of LA-SAPDs to quarterly usage patterns. However, we can say that most patients using LA-APDs will not need such use after a while, based on our clinical practice, although there is no study done in this field. With this study, we wanted to emphasize that while prescribing drugs used in the treatment of illnesses with psychotic symptoms, they should take into account the side effects of the drugs, as well as the daily, monthly, annual, and lifetime costs of the drugs. The principle of ‘using an effective drug recommended for a specific disorder at the required dose, in sufficient time, at the lowest cost’ adopted in the rational drug use guidelines should not be forgotten. It is expected that the modification of drug treatments, considering their costs as well as their efficiency, will contribute significantly to the country’s economy in the long run. Mustafa Yıldız1, Emre Osman2 REFERENCES American Psychiatric Association (2021) The American Psychiatric Association practice guideline for the treatment of patients with schizophrenia. Third edition. Washington, DC: American Psychiatric Association. Drug Prices. https://www.ilacrehberi.com/ilac-fihrist/ Accession date: 25th September 2020. National Institute for Health and Clinical Excellence (NICE) (2014) Psychosis and schizophrenia in adults: prevention and management. NICE Guideline CG178; https://www.nice.org.uk/guidance/cg178. Accession date: 4th April 2018. Öztürk MO, Uluşahin NA (2018) Mental Health and Disorders. 18th Edit. Ankara: Nobel Tıp Kitapevleri. (In Turkish) Republic of Turkey Central Bank Exchange Rates. https://www.tcmb.gov.tr/kurlar/kurlar_tr.html Accession date: 10th January 2021. Yıldız M (2005) The cost of treatment of psychotic disorders. Turk Psikiyatri Derg 16:146-7. (In Turkish) Yıldız M, Cerit C (2006) Annual cost of treatment for schizophrenia: Estimation from a university hospital data in Turkey. Bulletin of Clinical Psychopharmacology 16:239-44. Table 2. Comparison of the Annual Costs of Antipsychotic Drugs Calculated By The Daily Standard Average Dose Use, at Certain Price Ranges, for the Years 2005 and 2020 Price bracket (TRY) 2005 2020 500 ↓ Haloperidol tb, amp, Trifluoperazine drj, Chlorpromazine tb, Pimozid tb, Fluphenazine LAI Haloperidol tb, amp, depo, Trifluoperazine drj, Pimozid tb 500-1,000 Flupenthixol drj, LAI, Zuklopenthixol tb, acu, LAI, Sulpirid tb Chlorpromazine tb, Fluphenazine LAI, Flupenthixol drj, LAI, Clozapine tb, Risperidone tb 1,000-2,000 Clozapine tb, Risperidone tb Olanzapine tb, Sulpirid tb 2,000-3,000 Amisulpirid tb, Olanzapine tb, Quetiapine tb Zuklopenthixol tb, acu, LAI, Amisulpirid tb, Ziprasidone tb, Paliperidone tb, Aripiprazole tb 3,000-5,000 Ziprasidone tb Quetiapine tb 5,000-10,000 Risperidone consta Sertindole tb 10,000 ↑ Risperidone consta, Paliperidone monthly, Paliperidone 3 monthly, Aripiprazole maintana tb: Tablet, drj: Dragee, amp: Ampoule, LAI: Long-acting injectable, acu: Acuphase,