Browsing by Subject "Psychiatry"

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Now showing items 1-19 of 19
  • Levola, Jonna M.; Sailas, Eila S.; Saamanen, Timo S.; Turunen, Leena M.; Thomson, Annika C. (2019)
    Background: The focus of emergency room (ER) treatment is on acute medical crises, but frequent users of ER services often present with various needs. The objectives of this study were to obtain information on persistent frequent ER service users and to determine reasons for their ER service use. We also sought to determine whether psychiatric diagnoses or ongoing use of psychiatric or substance use disorder treatment services were associated with persistent frequent ER visits. Methods: A cohort (n = 138) of persistent frequent ER service users with a total of 2585 ER visits during a two-year-period was identified. A content analysis was performed for 10% of these visits. Register data including International Classification of Primary Care 2 (ICPC-2) -codes and diagnoses were analyzed and multivariable models were created in order to determine whether psychiatric diagnoses and psychosocial reasons for ER service use were associated with the number of ER visits after adjusting for covariates. Results: Patients who were younger, had a psychiatric diagnosis and engaged in ongoing psychiatric and other health services, had more ER visits than those who were not. Having a psychiatric diagnosis was associated with the frequency of ER visits in the multivariable models after adjusting for age, gender and ongoing use of psychiatric or substance use disorder treatment services. Reasons for ER-service use according to ICPC-2 -codes were inadequately documented. Conclusions: Patients with psychiatric diagnoses are overrepresented in this cohort of persistent frequent ER service users. More efficient treatments paths are needed for patients to have their medical needs met through regular appointments.
  • Lindgren, Maija; Jonninen, Minna; Jokela, Markus; Therman, Sebastian (2019)
    Background: We investigated whether psychosis risk symptoms predicted psychiatric service use using seven-year register follow-up data. Methods: Our sample included 715 adolescents aged 15-18, referred to psychiatric care for the first time. Psychosis risk symptoms were assessed with the Prodromal Questionnaire (PQ) at the beginning of the treatment. We assessed the power of the overall PQ as well as its positive, negative, general, and disorganized psychosis risk symptom factors in predicting prolonged service use. Baseline psychiatric diagnoses (grouped into 7 categories) were controlled for. Based on both inpatient and outpatient psychiatric treatment after baseline, adolescents were divided into three groups of brief, intermittent, and persistent service use. Results: Stronger symptoms on any PQ factor as well as the presence of a mood disorder predicted prolonged service use. All of the PQ factors remained significant predictors when adjusted for baseline mood disorder and multimorbidity. Conclusions: In a prospective follow-up of a large sample using comprehensive mental health records, our findings indicate that assessing psychosis risk symptoms in clinical adolescent settings at the beginning of treatment could predict long-term need for care beyond diagnostic information. Our findings replicate the previous findings that positive psychosis risk symptoms are unspecific markers of severity of psychopathology. Also psychosis risk symptoms of the negative, disorganization, and general clusters are approximately as strongly associated with prolonged psychiatric service use in the upcoming years.
  • Rissanen, Anne; Lindberg, Nina; Marttunen, Mauri; Sintonen, Harri; Roine, Risto (2019)
    BackgroundLittle is known about adolescents' perceptions about their health-related quality of life (HRQoL) in the course of routine adolescent psychiatric treatment. The aim of this 1-year follow-up study was to investigate HRQoL and changes in it among youths receiving adolescent psychiatric outpatient treatment.MethodsThe study comprised 158 girls and 82 boys aged 12-14years from 10 psychiatric outpatient clinics in one Finnish hospital district. Same-aged population controls (210 girls and 162 boys) were randomly collected from comprehensive schools. HRQoL was measured using the 16D instrument. The questionnaire was self-administered when the adolescents entered the polyclinics (=baseline), after a treatment period of 6months, and after 12months.ResultsThe mean age of respondents was 13.8years (SD 0.63). At baseline, the mean HRQoL score of both female and male outpatients was significantly lower than that of population controls (p
  • Rissanen, Anne; Lindberg, Nina; Marttunen, Mauri; Sintonen, Harri; Roine, Risto (BioMed Central, 2019)
    Abstract Background Little is known about adolescents’ perceptions about their health-related quality of life (HRQoL) in the course of routine adolescent psychiatric treatment. The aim of this 1-year follow-up study was to investigate HRQoL and changes in it among youths receiving adolescent psychiatric outpatient treatment. Methods The study comprised 158 girls and 82 boys aged 12–14 years from 10 psychiatric outpatient clinics in one Finnish hospital district. Same-aged population controls (210 girls and 162 boys) were randomly collected from comprehensive schools. HRQoL was measured using the 16D instrument. The questionnaire was self-administered when the adolescents entered the polyclinics (= baseline), after a treatment period of 6 months, and after 12 months. Results The mean age of respondents was 13.8 years (SD 0.63). At baseline, the mean HRQoL score of both female and male outpatients was significantly lower than that of population controls (p < 0.001). HRQoL of female patients was significantly worse than that of male patients (p < 0.001). In girls, HRQoL improved continuously during the 12-month follow-up, yet it remained worse than that of female population controls. Among boys, HRQoL was substantially better at the 6-month follow-up than at baseline, but this positive development was no longer seen at the 12-month follow-up. Conclusions From the perspective of HRQoL, girls seem to benefit more than boys from adolescent psychiatric outpatient treatment. Possible explanations for this finding are discussed.
  • Virtanen, Tomi; Eskelinen, Saana; Sailas, Eila; Suvisaari, Jaana (Helsingfors universitet, 2016)
    Background Constipation and dyspepsia are disturbing gastrointestinal symptoms that are often ignored in research on physical comorbidities of schizophrenia. Aims Our aim was to assess dyspepsia and constipation in a sample of outpatients with schizophrenia spectrum psychoses. Methods A general practitioner performed a thorough physical health check for 275 outpatients and diagnosed constipation and dyspepsia. We assessed the possible contribution of several sociodemographic, lifestyle, and clinical variables to constipation and dyspepsia using logistic regression analysis. We also assessed whether these symptoms were associated with abnormal laboratory findings. Results The prevalence of constipation was 31.3%, and of dyspepsia 23.6%. Paracetamol (OR=3.07, 95% CI 1.34–7.02) and clozapine use (OR=5.48, 95% CI 2.75–10.90), older age (OR=1.04, 95% CI 1.01–1.06), and living in sheltered housing (OR=2.49, 95% CI 1.16–5.33) were risk factors for constipation. For dyspepsia the risk factors were female sex (OR=2.10, 95% CI 1.15–3.83), non-steroidal anti-inflammatory drugs (OR=2.47, 95% CI 1.13–5.39), and diabetes medication (OR=2.42, 95% CI 1.12–5.25). Patients with dyspepsia had lower hemoglobin and hematocrit and higher glucose values than those without dyspepsia. Patients with constipation had lower thrombocyte values than patients without constipation. However, these findings were explained by factors predisposing to constipation and dyspepsia. Conclusions Clozapine use markedly increases the risk of constipation and may lead to life-threatening complications. In addition, analgesics and diabetes medication were related to gastrointestinal symptoms. These medications and their association to gastrointestinal symptoms should be kept in mind when treating patients with schizophrenia.
  • Komulainen, Emma (Helsingin yliopisto, 2019)
    Introduction: The mechanisms of action of antidepressants at the system level remain mainly unresolved. Antidepressants rapidly modulate emotional processing, enhancing processing of positive versus negative information, but this has been mostly demonstrated in healthy subjects and using fairly simple, controlled emotional stimuli such as emotional faces. Aim of the study: The aim of the studies of this thesis was to shed light on early antidepressant effects on emotional processing both in healthy subjects, avoiding the confounding effect of depressed mood, and in treatment-seeking depressed patients at an early stage of treatment, to elude the confounding effect of improved mood. The studies specifically aimed to reveal antidepressant effects on self-referential processing, a core factor in psychopathology of depression, and to investigate whether/how antidepressants modulate processing of complex, dynamic emotional stimuli resembling daily-life emotional situations. Methods: In Study 1 (experiments I and II), an open-label study of 30 healthy volunteers, half of the subjects received mirtazapine 15 mg two hours prior to functional magnetic resonance imaging (fMRI), and the other half was scanned without medication as a control group. Study 2 (experiments III and IV) was a double-blind, placebo-controlled study where 32 treatment-seeking depressed patients were randomized to receive escitalopram 10 mg or placebo for one week, after which fMRI was performed. In experiments I and III, neural responses to positive and negative self-referential adjectives as well as a neutral control task were assessed. In experiments II and IV participants listened to spoken emotional narratives and neural responses to the emotional content of the narratives were assessed. Results: Both mirtazapine in healthy subjects and escitalopram in depressed patients modulated self-referential processing. Mirtazapine attenuated responses to both positive and negative self-referential words in the anterior cortical midline structures (CMS, including the medial prefrontal cortex and the anterior cingulate), whereas escitalopram increased processing of positive relative to negative self-referential words. When comparing the placebo group and the escitalopram group from Study 2 separately with the healthy controls from Study 1, depressed patients receiving placebo had decreased responses of the anterior CMS to positive versus negative self-referential words, whereas no differences were found between the escitalopram group and healthy controls, implicating normalization of the negative bias in depressed patients receiving escitalopram. Both mirtazapine and escitalopram also modulated brain responses to spoken emotional narratives. Mirtazapine was found to modulate dynamic functional connectivity (measured with seed-based phase synchronization) of large-scale brain circuits, particularly potentiating functional connectivity of the anterior CMS and the limbic regions during positive parts of the narratives. Escitalopram increased synchronization of brain responses (measured with inter-subject correlation, ISC), specifically during positive parts of the narratives. Conclusions: A single dose of mirtazapine in healthy subjects and a one-week treatment with escitalopram in treatment-seeking depressed patients modulated neural responses to emotional information without any concurrent changes in mood. Both antidepressants modulated self-referential processing, a core psychological process in developing and maintaining depression. Escitalopram normalized the negatively biased self-referential processing of depressed patients in the anterior CMS. Both mirtazapine and escitalopram modulated brain responses to spoken emotional narratives, extending the previous findings of antidepressant effects based on simple emotional stimuli to complex, dynamic, every-day like emotional situations. Specifically, potentiated processing measured with novel methods of dynamic functional connectivity and ISC was found in the anterior CMS among other regions during positive emotional content of the narratives. These results suggest that antidepressants rapidly modulate processing of particularly positive emotional and self-referential information in the anterior CMS. This may be important for their later therapeutic effect.
  • Lönnqvist, Jouko; Achté, Anna-Maija (2019)
  • Weiste, Elina; Peräkylä, Anssi; Valkeapää, Taina; Savander, Enikö; Hintikka, Jukka (2018)
    Diagnosis is integral part of the way medicine organises illness: it is important for identifying treatment options, predicting outcomes and providing an explanatory framework for clinicians. Previous research has shown that during a medical visit not only the clinician but also patients provide explanations for the causes of their symptoms and health problems. Patients' lifeworld explanations are often differentiated from the diagnostic explanations provided by clinicians. However, while previous conversation analytic research has elaborated the ways in which diagnostic and lifeworld explanations are interactionally structured in somatic medicine, there is little research on how these explanations are organised in psychiatry. Psychiatric diagnosis is particularly interesting because in mental disorders illness itself is not determined by any objective measurement. Understanding of the patient's problem is constructed in interaction between the patient and clinician. The focus of this research will be patients' references to diagnosis in psychiatry and the functions of these references. The findings are based on conversation analysis of 29 audio-recorded diagnostic interviews in a psychiatric outpatient clinic. Our results demonstrate that patients can utilise diagnostic categories in several ways: disavowing a category to distance their symptoms from it, accounting for their life experiences being rooted in psychiatric illnesses and explaining their illnesses as being caused by certain life experiences. We argue that these explanations are important in patients' face-work - in constructing and maintaining a coherent and meaningful view of the patient's self.
  • Biswanger, O., Siemerling, E. toim. (Jena, 1915)
  • Bleuler, E. (Berlin, 1918)
  • Aarab, Ghizlane; Nikolopoulou, Maria; Ahlberg, Jari; Heymans, Martijn W.; Hamburger, Hans L.; de Lange, Jan; Lobbezoo, Frank (2017)
    The aim of this randomized placebo-controlled trail was to compare the effects of an objectively titrated mandibular advancement device (MAD) with those of nasal continuous positive airway pressure (nCPAP) and an intraoral placebo device on symptoms of psychological distress in OSA patients. In a parallel design, 64 mild/moderate OSA patients (52.0 +/- 9.6 years) were randomly assigned to an objectively titrated MAD, nCPAP, or an intraoral placebo appliance. All patients filled out the Symptom Checklist-90-Revised twice: one before treatment and one after 6 months of treatment. The Symptom Checklist-90-Revised is a multidimensional symptom inventory designed to measure symptomatic psychological distress over the past week. Linear mixed model analyses were performed to study differences between the therapy groups for the different dimensions of the Symptom Checklist-90-Revised over time. The MAD group showed significant improvements over time in the dimensions "somatization," "insufficiency of thinking and acting," "agoraphobia," "anxiety," "sleeping problems," and "global severity index" (F = 4.14-16.73, P = 0.048-0.000). These improvements in symptoms of psychological distress were, however, not significantly different from those observed in the nCPAP and placebo groups (P = 0.374-0.953). There is no significant difference between MAD, nCPAP, and an intraoral placebo appliance in their beneficial effects on symptoms of psychological distress. The improvement in psychological distress symptoms in mild/moderate OSA patients under MAD or nCPAP treatment may be explained by a placebo effect.
  • Laukkonen, Riina (Helsingfors universitet, 2015)
    Pakonomainen liikunta on yleinen ja tunnettu syömishäiriöihin liittyvä ilmiö, joka yhdistyy syömishäiriöiden vaikeampaan taudinkuvaan, huonompaan hoitotulokseen, hoidon keskeyttämiseen, pidempään sairaalahoitojaksoon ja merkittävästi suurentuneeseen sekä varhaisempaan uusiutumisriskiin. Pelkkä liikunnan runsas määrä tai rasittavuusaste ei kerro liikunnan olevan pakonomaista, vaan tarvitaan moniulotteinen määritelmä, joka huomioi myös liikunnan herättämät tunteet. Tarkoituksenani oli tutkia pakonomaisen liikunnan esiintyvyyttä ja erityispiirteitä suomalaisten sairaalahoitoisten syömishäiriöpotilaiden joukossa. Potilaiden liikuntamääriä ja liikunnan rasittavuusasteita kartoitettiin itse täytettävällä lomakkeella. Liikunnan pakonomaisuutta mitattiin Exercise dependence scale-revised (EDS-R) –lomakeen avulla. Laihuushäiriöpotilaat harrastivat keskimäärin vähemmän rasittavaa liikuntaa ahmimishäiriöpotilaisiin nähden. Potilaista 67%:a luokiteltiin pakonomaisiksi liikkujiksi ja heidän liikuntamäärät olivat noin kaksinkertaisia ei pakonomaisesti liikkuviin nähden. Potilaat, joilla oli taustalla aiempia sairaalahoitojaksoja liikkuivat määrällisesti enemmän ja saivat suurempia EDS-R-pisteitä ensimmäisellä hoitojaksolla oleviin potilaisiin verrattuna. EDS-R-kaavake voi olla jatkossa hyödyllinen mittari arvioitaessa syömishäiriöpotilaiden pakonomaisen liikunnan voimakkuutta.
  • Stubbs, Brendon; Koyanagi, Ai; Hallgren, Mats; Firth, Joseph; Richards, Justin; Schuch, Felipe; Rosenbaum, Simon; Mugisha, James; Veronese, Nicola; Lahti, Jouni; Vancampfort, Davy (2017)
    Background: Despite the known benefits of physical activity (PA) among people with anxiety, little is known about PA levels in people with anxiety at the population level. This study explored the global prevalence of anxiety and its association with PA. Methods: Cross-sectional, community-based data from the World Health Survey was analyzed. Prevalence of anxiety was estimated for 237,964 individuals (47 countries). PA was categorized as low, moderate, and high based on the International Physical Activity Questionnaire (short form). The association between PA and anxiety was assessed by multivariable logistic regression. Results: The overall global prevalence of anxiety was 11.4% (47 countries). Across 38 countries with available data on PA, 62.5%, 20.2%, and 17.3% of the sample engaged in high, moderate, and low levels of PA respectively. The prevalence of low physical activity in those with and without anxiety was 22.9% vs. 16.6% (p <0.001) (38 countries, n=184,920). In the pooled model adjusted for socio-demographics, depression, and country, individuals engaging in low PA (vs. high PA) had 1.32 (95% CI=1.17-1.47) times higher odds for anxiety than those with high PA. Female sex, older age, lower education and wealth, and depression were also associated with low PA. At the individual country level, there was a significant positive association between low PA and anxiety in 17 of the 38 countries. Conclusion: Low PA levels are associated with increased prevalence of anxiety. There is a need for longitudinal research to establish the directionality of the relationships observed.
  • Hernberg, Sofia; Lehto, Soili; Raij, Tuukka (Helsingin yliopisto, 2020)
    Insikt om mental hälsa och psykiatrisk vård har ökat kraftigt under senaste åren, men trots framsteg är den samhälleliga bördan av mentala sjukdomar fortfarande stor. Ytterligare utveckling inom psykiatri kräver aktiv, högklassig forskning och för att rikta forskningen till rätt mål, krävs aktuell information om forskningsfältet. Målet med denna studie var att undersöka trender i finsk psykiatriforskning, vilket vi gjorde genom att söka och evaluera artiklar i MEDLINE-databasen. Vi sökte artiklar med insatser av forskare från finska organisationer och som publicerats år 2019 inom psykiatri. Vi undersökte vilka ämnen det forskats i och var artiklarna publicerats. Därtill jämförde vi de olika forskningsanstalterna med varandra och gjorde internationell jämförelse av våra resultat. Sammanlagt mötte 415 artiklar våra kriterier. Den mest undersökta ICD-10-kategorin var F30-39 och den mest undersökta sjukdomen var depression. Andra vanliga forskningsområden var schizofreni, missbruk av rusmedel och ångest. Majoriteten av artiklarna var publicerade i journaler med låg Publikationsforum-klassificering (JUFO-klassificering). Samtidigt tyder data från tidigare år på att antalet artiklar i journaler med hög impact factor är betydligt lägre i Finland än i andra nordiska länder, vilket borde undersökas vidare i framtida studier. Forskningsområdena verkar möta samhällets behov väl, medan forskningens inverkan torde förbättras genom att publicera mera artiklar i journaler med högre impact factor/ JUFO-klassificering.
  • Levola, Jonna; Niemelä, Solja; Kuurne, Kaisa; Aalto, Mauri; Simojoki, Kaarlo; Alho, Hannu (2019)
    Riippuvuussairauksien hoitoon ei ole nykyisellään tarpeeksi osaavia lääkäreitä eikä resursseja. Tehokkain tapa kuroa vajetta kiinni olisi päihdelääketieteen erikoislääkärikoulutuksen käynnistäminen 2020-luvulla.
  • Saarinen, Tiina (Helsingfors universitet, 2017)
    Nykypäivänä noin viidennes nuorista sairastaa vuositasolla jotakin mielenterveyshäiriötä ja moni heistä myös useampaa häiriötä samaan aikaan. Mielenterveyden häiriöt altistavat itsetuhoisuudelle ja mielenterveyshäiriöiden samanaikaissairastavuus lisää riskiä entisestään. Mielenterveyshäiriöitä on pyritty luokittelemaan erilaisin tavoin ja yksi tapa jakaa oireita on ollut ryhmitellä oireilu isompiin emotionaalisen ja käyttäytymisen oireilun ryhmiin. Tästä jaosta voidaan käyttää myös termejä sisäänpäin ja ulospäin suuntautuneet oireet tai häiriöt. Tässä tutkimuksessa tutkittiin itsetuhoisuutta em. mukaisesti sisäänpäin ja ulospäin suuntautuneista mielenterveyden häiriöistä sekä näiden yhdistelmistä kärsivillä nuorilla. Tutkimuksessa vertailtiin sekä nuorisopsykiatrisia potilaita ja verrokkeja että potilaita keskenään. Aineisto koostuu "Nuorisopsykiatrisen osastohoidon kehittämis- ja tutkimushanke Kellokosken sairaalassa" (The Kellokoski Hospital Adoslescent Follow-up study, Kaifus) – hankkeeseen kerätystä materiaalista. Osastohoitopotilailla oli luonnollisesti huomattavan paljon enemmän itsetuhoisuutta kuin verrokeilla (p < 0,001). Selvä itsetuhoisuus, eli itsemurhasuunnitelmat ja -yritykset, ja ylipäätään itsetuhoisuus oli yhteydessä enemmän sisäänpäin suuntautuneisiin häiriöihin kuin puhtaasti ulospäin suuntautuneisiin häiriöihin.
  • Kaartinen, Markku (Helsingfors universitet, 2014)
    Tutkimuksen tarkoituksena oli selvittää, kuinka vakavien mielenterveyshäiriöiden hoito toteutui Helsingin kaupungin psykiatrisessa erikoissairaanhoidossa vuosina 2008-2009. Satunnaisesti valitun 168:n helsinkiläisen masennusta, kaksisuuntaista mielialahäiriötä ja skitsofreniaa sairastavan potilaan sairauskertomusmerkinnät käytiin läpi. Potilaiden sosiodemografiset tekijät (siviilisääty, koulutus, yksin asuminen ja työssäkäynti) selvitettiin. Hoidon sisältöä verrattiin voimassa olleisiin "Käypä-hoito"-suosituksiin (KH). Potilaat jakaantuivat kutakuinkin tasan eri diagnoosiryhmien kesken. Tutkimuksessa pyrittiin myös selvittämään oliko hoitokäytännöillä eroja kaupungin viidellä psykiatrisella poliklinikalla ja vaikuttiko potilaan asuinalue ja sosioekonominen asema mahdollisesti hänen saamaansa hoitoon. Spesifien ei-lääkkeellisten hoitomenetelmien (psykoedukaatio, psykoterapia, ECT=electric convulsive treatment, aivojen sähköhoito) ja erilaisten kyselykaavakkeiden ja oiremittareiden käyttö oli alueilla kirjavaa ja kaiken kaikkiaan sangen vähäistä. Noin kolmella potilaalla neljästä (73.2%) oli voimassa oleva kirjallinen hoitosuunnitelma. Lääkehoito toteutui KH-suositusten mukaisesti noin kahdella potilaalla kolmesta (66.1%). Potilaille määrättiin kaikissa diagnoosiryhmissä useimmiten (78 kpl, 46.4%) 3-5 eri psyykenlääkettä. Neljällä masennuspotilaalla (7.3%:lla masennuspotilaista) ei ollut mitään lääkitystä. Lääkärikäyntien lukumäärä oli keskimärin 4.8 käyntiä tutkimusjakson aikana. Kuusi potilasta (3.6%) ei tavannut lääkäriä kertaakaan. Depressiodiagnoosilla psykiatrian poliklinikoilla hoidossa olleista tarvitsi seuranta-aikana ainakin kerran sairaalahoitoa 7.2%, kaksisuuntaista mielialahäiriötä sairastavista 22.2.% ja skitsofreniapotilaista 62.7%. Koko aineistossa vähiten sairaalahoitoa tarvitsivat korkeasti koulutetut (akateemiset) potilaat (13.7%). Vain peruskoulun käyneistä lähes joka toinen (48.6%) päätyi ainakin kerran sairaalahoitoon, noin joka viides (22.1%) keskiasteen koulutuksen saaneista ja opiskelijoista (21.5%). Voimassa olevan hoitosuunnitelman puuttuminen noin joka neljänneltä potilaalta, psykiatristen arviointiasteikoiden vähäinen ja alueiden sisälläkin epäyhtenäinen käyttö sekä lääkehoidon epäasianmukaisuus merkittävällä osalla potilaita olivat suurimmat puutteet. Asuinalue ei pääsääntöisesti vaikuttanut potilaiden saamaan hoitoon. Kuitenkin alueiden välillä oli joidenkin muuttujien kohdalla tilastollisesti merkitseviä eroja (puuttuva hoitosuunnitelma, oireenhallintakurssien käyttö, lääkäreiden puhelinvastaanottotoiminta, korkeasti koulutettujen osuus poliklinikan potilaista). Korkeammin koulutetut joutuivat harvemmin sairaalahoitoon kuin vähemmän koulutetut. Yksin asuvat joutuivat useammin (yksi neljästä) sairaalahoitoon kuin ei-yksin asuvat (yksi kolmesta). Kansalliset hoitosuositukset (KH) suosittavat psykiatristen arviointiasteikkojen käyttöä ja näiden osuutta hoidossa tulisi lisätä ja yhdenmukaistaa eri alueilla ja työntekijöillä. Hoitosuunnitelma tulisi olla kirjattuna potilaskertomukseen. Lääkehoidossa olisi pyrittävä hoitosuositusten mukaisiin vaikuttaviksi osoitettuihin annoksiin.