Uutta tutkimustietoa psykososiaalisesta hoidosta psykoosien hoidossa: Ihmisen kokonaisvaltaisella kohtaamisella ja verkostokeskeisellä hoidolla pysyvämpiä tuloksia kuin psykoosilääkehoidolla Jaakko Seikkula 16.2.2018
Skitsofrenian käypä hoito- Duodecim Psykoosilääkkeiden teho positiivisten oireiden hoidossa ja uusien psykoosivaiheiden estossa on osoitettu vakuuttavasti kontrolloiduissa tutkimusasetelmissa 122. Skitsofrenian käypä hoito suosituksessa ei viitata tutkimuksiin, jossa olisi verrattu lääkehoidon ja ei lääkehoidon eroja. Lääkehoidon tärkeyteen viitataan Tiihonen yms. 2011 observaatio tutkimukseen, joka ei ole kontrolloitu koeasetelma tutkimus
Skitsofrenian käypä hoito - Duodecim Psykoosin ennakko-oireista kärsivien hoidossa on suositeltu vaiheittain etenevää hoitomallia 28, 37: Alkuvaiheen ennakko-oireilevia tulisi hoitaa kognitiivis-behavioraalisella tai tukea-antavalla psykoterapialla ja oireenmukaisella ahdistus- ja mielialalääkityksellä. Välittömään riskivaiheeseen edenneillä psykoterapeuttisen hoidon ohella voidaan käyttää psykoosilääkkeitä pieninä annoksina. Psykoosilääkityksen aloittaminen perustuu aina yksilölliseen potilaan tilanteen arvioon on hoidon alkuvaiheessa aiheellista positiivisten oireiden lievittämiseksi. Ellei ensipsykoosipotilaan skitsofreniadiagnoosi ole varma, lääkehoidon aloitusta voidaan siirtää 1 2 viikkoa, koska osa potilaista toipuu ilman psykoosilääkitystä.
Lääkehoidon tutkimusvaihtoehdot 1. Satunnaistetut abruption kokeet: Psykoosilääke kaikille 6 kk 1v, jonka jälkeen satunnaistetaan lääkehoito- ja lumelääkeryhmään (Leucht ym. 2012 Meta-analyysi N=67 ) 2. Todelliset satunnaistetut kokeet: Heti hoidon alussa lääke vs lumelääke ryhmät (Bola ym. 2014 Meta-analyysi N=5) 3. Observaatiotutkimukset ja kvasikokeelliset asetelmat - Tiihonen ym. 2009 - Pohjois-Suomen kohortti: Joukamaa ym 2006, Moilanen ym., 2014 4. Lääkityksen tarpeenmukainen käyttö: API, ODAP, Soteria tutkimukset
1. Satunnaistetut kokeet, jossa neuroleptilääkitys keskeytetään Leucht S, Tardy M, Komossa K, Heres S, Kissling W, Salanti G, et al. Antipsychotic drugs versus placebo for relapse prevention in schizophrenia: a systematic review and meta-analysis. Lancet 2012; 379: 2063 71. (116 suitable from 65 trials, N=6493 patients) The primary outcome was relapse between 7 and 12 months. Other outcomes were readmission, dropout, improvement of disease, death, violence or aggressive behaviour, adverse events, quality of life, satisfaction with care, and employment.
1. Satunnaistetut kokeet, jossa neuroleptilääkitys keskeytetään. Leucht S, Tardy M, Komossa K, Heres S, Kissling W, Salanti G, et al. Antipsychotic drugs versus placebo for relapse prevention in schizophrenia: a systematic review and meta-analysis. Lancet 2012; 379: 2063 71. (116 suitable from 65 trials, N=6493 patients) Antipsychotic drugs significantly reduced relapse rates at 1 year (drugs 27% vs placebo 64%; risk ratio [RR] 0 40, 95% CI 0 33 0 49; number needed to treat to benefit [NNTB] 3, 95% CI 2 3). Fewer patients given antipsychotic drugs than placebo were readmitted (10% vs 26%; RR 0 38, 95% CI 0 27 0 55; NNTB 5, 4 9), but less than a third of relapsed patients had to be admitted. Limited evidence suggested better quality of life (standardised mean difference 0 62, 95% CI 1 15 to 0 09) and fewer aggressive acts (2% vs 12%; RR 0 27, 95% CI 0 15 0 52; NNTB 11, 6 100) with antipsychotic drugs than with placebo. More patients given antipsychotic drugs than placebo gained weight (10% vs 6%; RR 2 07, 95% CI 2 31 3 25), had movement disorders (16% vs 9%; 1 55, 1 25 1 93), and experienced sedation (13% vs 9%; 1 50, 1 22 1 84). In subgroup analyses, number of episodes, whether patients were in remission, abrupt or gradual withdrawal of treatment, length of stability before trial entry, first-generation or secondgeneration drugs, and allocation concealment method did not significantly affect relapse risk. Depot preparations reduced relapse (RR 0 31, 95% CI 0 21 0 41) more than did oral drugs (0 46, 0 37 0 57; p=0 03) In a meta-regression, the difference between drug and placebo decreased with study length.
(RR 0 39, 95% CI 0 27 0 56; RD 0 18, 95% CI 0 09 0 26).
(RR 0 39, 95% CI 0 27 0 56; RD 0 18, 95% CI 0 09 0 26).
Robin M. Murray, Diego Quattrone, Sridhar Natesan, Jim van Os, Merete Nordentoft, Oliver Howes, Marta Di Forti and David Taylor. Should psychiatrists be more cautious about the long-term prophylactic use of antipsychotics? The British Journal of Psychiatry (2016) 209, 361 365. Thus, a meta-analysis of 65 trials 3 concluded that antipsychotic maintenance treatment substantially reduces relapse risk in all patients with schizophrenia for up to 2 years of follow-up. Leucht et al (2012): nothing is known about the very long-term effects of antipsychotic drugs compared to placebo Thus, long term maintenance treatment with antipsychotics is based on hope rather than evidence.
Tutkimusasetelman ongelmat: Validiteetti pieni Taylor M, Cavanagh J, Hodgson R, Tiihonen J. Examining the effectiveness of antipsychotic medication in first-episode psychosis. J Psychopharmacol 2012; 26: 27 32 RCTs measure efficacy, but the controlled environment of a RCT affects the generalisability of the results in the real world, especially when high drop-out rates, short trial duration, and the selection bias in patient recruitment are considered (Hodgson et al., 2007; Thornley and Adams, 1998). The drop-out rates of even relatively brief RCTs in medication trials in psychiatry can be up to 70% or even 80%, confounding the applicability of the results. In addition, large multicentre RCTs are expensive to conduct, which militates against undertaking long-term or maintenance studies.
Eri psykoosilääkkeiden tehon vertailu. Leucht et al., 2012b When considering the various antipsychotic trials in first- episode psychosis populations, despite their methodological differences, the EUFEST, Tiihonen et al. and Gau et al. studies appear to have some broadly similar results, with some but not all of the SGA (particularly olanzapine) being found to be more effective than FGA (particularly lowdose haloperidol). The CAFÉ study did not find a similar pattern of differential effectiveness. This lack of difference in terms of effectiveness, and indeed efficacy, has been echoed in the findings of a meta-analysis of 15 RCTs of antipsychotic medication in first-episode psychosis populations (Crossley et al., 2010) which did not find any statistically significant difference in efficacy or effectiveness between FGA and SGA. Equally important has been the observation that not using any antipsychotic medication after a first episode of psychosis significantly increases the risk of both all-cause death and suicide in these already pernicious illnesses (Tiihonen et al., 2006). In view of these conflicting studies, the British Association of Psychopharmacology (Barnes, 2011) guideline on the treatment of schizophrenia focuses on side effects rather than differential efficacy, and recommends low starting doses in first-episode psychosis with careful side effect monitoring
Satunnaistetut kokeet, pidempi seuranta-aika!) NORTHWICK PARK STUDY: Johnstone, E., Macmillan, F., et al. (1990) Further investigation of predictors of outcome following first schizophrenic episode. British Journal of Psychiatry, 157, 182-189. N= 253. Two year follow-up Neuroleptics Placebo p Variable ---------------------------------------------------------------------------- Relapses % 42% / 56 58% /62 <.01 (N= 118) Employment status 4 /175 9 /62 <.01 improved (N= 237) ----------------------------------------------------------------------------
Satunnaistettu lääkehoidon keskeytys pitkä seuranta-aika. 2) Wunderink, L., Nieboer, R.M., Wiersma, D., Sytema, S., Nienhuis, F.J., 2013. Recovery in remitted first-episode psychosis at 7 years of follow-up of an early dose reduction/ discontinuation or maintenance treatment strategy long-term follow-up of a 2- year randomized clinical trial. JAMA Psychiatry. 2013;70(9):913-920. doi:10.1001/jamapsychiatry.2013.19 Patients seen for the first time in mental health care services with a first episode of psychosis from October 1, 2001, until December 1, 2002 (N = 257), in a 3.2 million population catchment area. Of these, 111 patients refused to participate or were lost to 2 year follow-up, and 18 patients did not show response of symptoms within 6 months of antipsychotic treatment or sustained symptom remission during 6 months. Tarkoittaa: Potilaat satunnaistettiin 6 kk hoidon jälkeen eri ryhmiin
From: Recovery in Remitted First-Episode Psychosis at 7 Years of Follow-up of an Early Dose Reduction/Discontinuation or Maintenance Treatment StrategyLong-term Follow-up of a 2-Year Randomized Clinical Trial JAMA Psychiatry. 2013;70(9):913-920. doi:10.1001/jamapsychiatry.2013.19 Table Title: Recovery, Symptomatic Remission, and Functional Remission After 7 Years of Follow-up Date of download: 1/14/2018 Copyright 2013 American Medical Association. All rights reserved.
Wunderink, L., Nieboer, R.M., Wiersma, D., Sytema, S., Nienhuis, F.J., 2013. Recovery in remitted firstepisode psychosis at 7 years of follow-up of an early dose reduction/ discontinuation or maintenance treatment strategy long-term follow-up of a 2-year randomized clinical trial The results of this study lead to the following conclusions: 1) schizophrenia treatment strategy trials should include recovery or functional remission rates as their primary outcome and should also include long-term follow-up for more than 2 years, even up to 7 years or longer. 2) In the present study, short-term drawbacks, such as higher relapse rates, were leveled out in the long term, and benefits that were not evident in short-term evaluation, such as functional gains, only appeared during long-term monitoring.
2. Todelliset satunnaistetut kokeet John R. Bola, Dennis T. Kao and Haluk Soydan: Antipsychotic Medication for Early-Episode Schizophrenia Cochrane Database Syst Rev. Author manuscript; available in PMC 2014 July 22. N= 6; 1118 potilasta. People treated with a typical antipsychotic medication are less likely to leave the study early than those treated with placebo (chlorpromazine: 3RCTs,N= 353,RR0.4, 95%CI 0.3 0.5,NNT = 3.2; Two studies reported a general pattern of more frequent adverse effects for people treated with typical antipsychotic medications compared with placebo. One study reported a higher rehospitalization rate for those receiving chlorpromazine compared with placebo (N= 80,RR2.29, 95%CI 1.3 4.0,NNH = 2.9); however, higher attrition in the placebo group is likely to have introduced a survivor bias (N = 127, RR 1.69, 95% CI 0.9 3.0). One study contributed data to a comparison of trifluoperazine with psychotherapy on long-term health and favored the trifluoperazine group (n = 92, MD Meninger Health Sickness Scale 5.8, 95% CI 1.6 0.0). One study found no between-group differences comparing typical antipsychotic medication with psychosocial treatment on 6-week outcome measures of global psychopathology (N = 89,MD Global Psychopathology Scale 0.01, 95% CI 0.6 to 0.6) and global improvement (N= 89, MD Global Improvement Scale 0.03, 95% CI 0.5 to 0.4), indicating no between group differences. Preliminary evidence suggests that initial antipsychotic treatment may reduce attrition while also increasing the risk for medication-induced adverse effects.
3. Observation tutkimukset ja kvasikokeelliset asetelmat Observational studies assess effectiveness, namely whether a treatment or intervention works in the real world of day-to-day clinical practice. It has been shown (Mallinckrodt et al., 2003) that well-constructed observational studies do not overestimate treatment effects, and statistical methodologies can reduce the impact of non-randomisation. In addition, the lack of exclusion criteria can reduce selection bias (although this remains a concern), enhancing the utility of the results, particularly in large community-based samples. Observational studies are also generally much cheaper than RCTs, so can often be undertaken independent of any vested commercial interest. (Taylor et al., 2012)
11-year follow-up of mortality in patients with schizophrenia: a population-based cohort study (FIN11 study) Jari Tiihonen, Jouko Lönnqvist, Kristian Wahlbeck, Timo Klaukka, Leo Niskanen, Antti Tanskanen, Jari Haukka Lancet: www.thelancet.com Published online July 13, 2009 Nationwide registers in Finland were used to compare the cause-specific mortality in 66 881 patients versus the total population (5 2 million) between 1996, and 2006, and to link these data with the use of antipsychotic drugs. We measured the all-cause mortality of patients with schizophrenia in outpatient care during current and cumulative exposure to any antipsychotic drug versus no use of these drugs. Although the proportional use of second-generation antipsychotic drugs rose from 13% to 64% during followup, the gap in life expectancy between patients with schizophrenia and the general population did not widen between 1996 (25 years), and 2006 (22 5 years). Compared with current use of perphenazine, the highest risk for overall mortality was recorded for quetiapine (adjusted hazard ratio [HR] 1 41, 95% CI 1 09 1 82), and the lowest risk for clozapine (0 74, 0 60 0 91; p=0 0045 for the difference between clozapine vs perphenazine, and p<0 0001 for all other antipsychotic drugs). Long-term cumulative exposure (7 11 years) to any antipsychotic treatment was associated with lower mortality than was no drug use (0 81, 0 77 0 84). In patients with one or more filled prescription for an antipsychotic drug, an inverse relation between mortality and duration of cumulative use was noted (HR for trend perexposure year 0 991; 0 985 0 997).
11-year follow-up of mortality in patients with schizophrenia: a population-based cohort study (FIN11 study) Jari Tiihonen, Jouko Lönnqvist, Kristian Wahlbeck, Timo Klaukka, Leo Niskanen, Antti Tanskanen, Jari Haukka Lancet: www.thelancet.com Published online July 13, 2009 In total, 84 patients died during follow-up, mortality was more than 10 times higher in patients not taking drugs than in patients currently taking antipsychotic drugs: 75 patients not taking drugs died (3362 person years) and nine patients taking drugs died (4664 person years) (adjusted relative risk 12.3, 6.0 to 24.1, corresponding to population attributable risk of 83%, 68% to 91%). Twenty six suicides occurred in patients not taking drugs compared with one suicide in patients taking drugs (crude relative risk 36.1,4.9 266;adjusted relative risk37.4,5.1to276).the corresponding figures for all unnatural deaths (suicides, violence, accidents) were 51 per 3362 person years and five per 4664 person years (14.1, 5.6 35.4) and for all natural deaths 24 per 3362 person years and four per 4664 person years (8.3,2.9 24.0).
Tutkimuksen kritiikki: Tutkimusasetelma ei oikeuta tehtyihin johtopäätöksiin Marc De Hert, Christoph U. Correll, and Dan Cohen Do antipsychotic medications reduce or increase mortality in schizophrenia? A critical appraisal of the FIN-11 study. Schizophrenia Research 117 (2010) 68 74 The following variables were not available: marital status, substance abuse diagnosis, socio-economic status, (un) healthy lifestyle variables, detailed cardiovascular history and risk assessment data Since suicide occurs earlier in the illness course, this represents a very strong and systematic cohort effect, which might not be amenable to efforts of statistical control via complicated statistical methodology (De Hert et al., 2009b). Rather, a confirmatory sensitivity analysis should have been performed as well, matching all antipsychotic groups on illness duration. Tutkimuksessa ei anneta mitään tietoa potilasryhmistä. Ei lääkitys ryhmää ei verrata lääkitysryhmään. Niinpä ei ole tietoa, mitkä tekijät vaikuttavat lääkehoidon toteutumiseen. Sairaalahoidon aikana kuolleet jätetty pois tilastoista vaikuttanee erityisesti itsemurhien määrään
Marc De Hert, Christoph U. Correll, and Dan Cohen Do antipsychotic medications reduce or increase mortality in schizophrenia? A critical appraisal of the FIN-11 study. Schizophrenia Research 117 (2010) 68 74 Tiihonen and colleagues (2009) report that 18,914 patients with schizophrenia had not received any antipsychotic drug during the mean follow-up of 7.8 years (146,930 person-years). It seems somewhat unlikely that 28.2% of the total number of patients would never have used antipsychotics nor have been hospitalized for a relapse during the follow-up period. Previous studies from the same authors on smaller cohorts found indeed that a substantial number of these patients were taking antipsychotic medications at some time during follow-up (49% and 96%) (Tiihonen et al., 2006b; Haukka et al., 2008), and that 21% were admitted during a much shorter follow-up of only 3.6 years (Table 1). Another Finnish study on the effect of the decreasing number of psychiatric beds found that less than 4% of the patients were not in psychiatric care (Salokangas et al., 2002). Finally, since the registry does not record medications dispensed during hospitalization, antipsychotic exposure during hospitalization was not counted in this study. Keskimäärin 50 sairaalahoitopäivää: Todennäköisesti lähes kaikki potilaat saaneet psykoosilääkitystä noin 2 kuukauden ajan ja sairaalahoidon jälkeen eivät ottaneet heille määrättyä lääkitystä
Marc De Hert, Christoph U. Correll, and Dan Cohen Do antipsychotic medications reduce or increase mortality in schizophrenia? A critical appraisal of the FIN-11 study. Schizophrenia Research 117 (2010) 68 74 comparison with the mortality rates in other studies underscores this point: with 5.69/1000 person years, the mortality for clozapine was, the lowest in the study by Tiihonen et al. (2009). By contrast, in other studies the mortality rates for clozapine were 8.5 (Taylor et al., 2009), 11.3 (Munro et al., 1999) and 12.5 (Meltzer et al., 2003), as well as 4.6 for persons under 55 years and 45.6 for persons over 55 years (Walker et al., 1997). It is unclear whether the considerably lower mortality risk with clozapine is a true effect or whether it is the result of the chosen methodology. For a fair judgment of the resulting death risks, a calculation of the effect of the one-sidedness of the chosen methodology is needed.
Joukamaa M, Heliovaara M, Knekt P, Aromaa A, Raitasalo R, Lehtinen V. Pohjois-Suomen kohortti tutkimus: Kaikki v 1966 mukaan tutkimukseen, jossa seurataan laajasti terveydentilan kehitystä. Schizophrenia, neuroleptic medication and mortality. Br J Psychiatry. 2006 Feb;188:122-7. Pohjois-Suomen 1966 kohorttitutkimus During a 17-year follow-up, 39 of the 99 people with schizophrenia died. Adjusted for age and gender, the relative mortality risk between those with schizophrenia and others was 2.84 (95% CI 2.06-3.90), and was 2.25 (95% CI1.61-3.15) after further adjusting for somatic diseases, blood pressure, cholesterol, body mass index, smoking, exercise, alcohol intake and education. The number of neuroleptics used at the time of the baseline survey showed a graded relation to mortality. Adjusted for age, gender, somatic diseases and other potential risk factors for premature death, the relative risk was 2.50 (95% CI1.46-4.30) per increment of one neuroleptic.
Moilanen J, Haapea M, Miettunen J, Jaaskelainen E, Veijola J, Isohanni M, et al. Characteristics of subjects with schizophrenia spectrum disorder with and without antipsychotic medication a 10-year follow-up of the Northern Finland 1966 Birth Cohort study. Eur Psychiatry 2013; 28: 53 8. OBJECTIVE: To estimate the prevalence of non-medicated subjects having schizophrenia spectrum disorder and to study how they differ from medicated subjects in terms of sociodemographic and illness-related variables. We also aim to find the predictors for successful antipsychotic withdrawal. METHODS: Data of 70 subjects with schizophrenic psychoses (mean duration of illness 10.4 years) from the Northern Finland 1966 Birth Cohort were gathered by interview at the age of 34 and from hospital records. The stability of remission was assessed by comparing hospitalization rates between non-medicated and medicated subjects over an 8.7-year additional follow-up period. RESULTS: Twenty-four (34%) subjects were currently not receiving medication. They were more often males, less often on a disability pension, more often in remission, and had better clinical outcomes. Relapses during the follow-up were equally frequent between non-medicated and medicated subjects (47% vs. 56%). Not having been hospitalised during previous 5 years before the interview predicted long-term successful antipsychotic withdrawal without relapse. CONCLUSIONS: Despite a lack of precise predictors, there might be subgroup of schizophrenia spectrum subjects who do not need permanent antipsychotic medication, and a fewer previous psychiatric treatments may indicate such a subgroup.
Martin Harrow, Thomas H. Jobe, Robert N. Faull, Jie Yang. 20-Year multi-follow-up longitudinal study assessing whether antipsychotic medications contribute to work functioning in schizophrenia. Psychiatry Research, 256, 267-274 To assess the long-term effectiveness of antipsychotic medications in facilitating work functioning in patients with schizophrenia we conducted longitudinal multi follow-up research on 139 initially psychotic patients. The sample of 25 patients with schizophrenia always prescribed antipsychotics and the sample of 15 schizophrenia patients not prescribed antipsychotics from the 2 year follow-ups onward allow longterm, multi-year, comparisons of patients with schizophrenia not on antipsychotics for many years with patients with schizophrenia continuously prescribed antipsychotics over a 20 year period. While antipsychotics reduce or eliminate flagrant psychosis for most patients with schizophrenia at acute hospitalizations, four years later and continually until the 20 year follow ups, patients with schizophrenia not prescribed antipsychotics had significantly better work functioning. The work performance of the patients who were continuously prescribed antipsychotics was at a low rate and did not improve over time. Multiple other factors also interfere with work functioning. The data suggest that some patients with schizophrenia not prescribed antipsychotics for prolonged periods can function relatively well. Multiple other factors are associated with poor post-hospital work performance. The longitudinal data raise questions about prolonged treatment of schizophrenia with antipsychotic medications.
Fig. 1. 20 Year longitudinal assessment of work functioning in schizophrenia: medicated and unmedicated patients. 1.Download high-res image (260KB) 2.Download full-size image Fig. 1. 20 Year longitudinal assessment of work functioning in schizophrenia: medicated and unmedicated patients.
Combination of antipsychotic medications and psychosis in schizophrenia: relation to work functioning at 20 year assessments. 1.Download high-res image (175KB) 2.Download full-size image
4. Psykoosilääkkeen tarpeenmukainen käyttö erityisissä hoito-ohjelmissa A.Bola JR 1, Mosher LR.Treatment of acute psychosis without neuroleptics: two-year outcomes from the Soteria project. J Nerv Ment Dis. 2003 Apr;191(4):219-29. Soteria provided predominantly extramedical treatment, employing a developmental crisis approach to recovery from psychosis. Treatment involved a small, homelike, intensive, interpersonally focused therapeutic milieu with a nonprofessional staff that expected recovery and related with clients in ways that do not result in the invalidation of the experience of madness (Mosher and Menn, 1978a, p 716). Antipsychotic medications were ordinarily not used during the first 6 weeks of treatment. However, there were explicit criteria for their shortterm use during this period; 76% (62 of 82) received no antipsychotic medications during the initial 45-day period. After 6 weeks, medication prescription decisions were made at a treatment conference that included the client, staff, and the consulting psychiatrist. A manual describing Soteria treatment in greater detail has been published in German (Mosher et al., 1994).
4. Psykoosilääkkeen tarpeenmukainen käyttö erityisissä hoito-ohjelmissa A.Bola JR 1, Mosher LR.Treatment of acute psychosis without neuroleptics: two-year outcomes from the Soteria project. J Nerv Ment Dis. 2003 Apr;191(4):219-29. The Soteria project (1971 1983) compared residential treatment in the community and minimal use of antipsychotic medication with usual hospital treatment for patients with early episode schizophrenia spectrum psychosis. Newly diagnosed DSM-II schizophrenia subjects were assigned consecutively (1971 to 1976, N = 79) or randomly (1976 to 1979, N = 100) to the hospital or Soteria and followed for 2 years. Multivariate analyses evaluated hypotheses of equal or better outcomes in Soteria on eight individual outcome measures and a composite outcome scale in three ways: for endpoint subjects (N = 160), for completing subjects (N = 129), and for completing subjects corrected for differential attrition (N = 129). Endpoint subjects exhibited small to medium effect size trends favoring experimental treatment. Completing subjects had significantly better composite outcomes of a medium effect size at Soteria (+.47 SD, p =.03). Completing subjects with schizophrenia exhibited a large effect size benefit with Soteria treatment (+.81 SD, p =.02), particularly in domains of psychopathology, work, and social functioning. Soteria treatment resulted in better 2-year outcomes for patients with newly diagnosed schizophrenia spectrum psychoses, particularly for completing subjects and for those with schizophrenia. In addition, only 58% of Soteria subjects received antipsychotic medications during the follow-up period, and only 19% were continuously maintained on antipsychotic medications.
On the whole, these data argue that a relationally focused therapeutic milieu with minimal use of antipsychotic drugs, rather than drug treatment in the hospital, should be a preferred treatment for persons newly diagnosed with schizophrenia spectrum disorder. We think that the balance of risks and benefits associated with the common practice of medicating nearly all early episodes of psychosis should be reexamined. In addition, the search, begun earlier, for treatment response subtypes in schizophrenia spectrum disorders (Carpenter and Heinrichs, 1981), particularly for patients not benefiting from antipsychotic medications, should be resumed. 3, 4
4. Psykoosilääkkeen tarpeenmukainen käyttö erityisissä hoito-ohjelmissa Lehtinen V, Aaltonen J, Koffert T, Rikkolainen V, Syvalahti E, Vuorio K. Integrated treatment model for first-contact patients with a schizophrenia-type psychosis: The Finnish API project. Nord J Psychiatry 1996;50:281-287. Oslo. ISSN 0803-9488. Rather simple hypothesis concerning the significance of neuroleptics in the treatment of acute schizophrenic and other nonaffective psychoses. The new patients in these diagnostic categories can be divided in three groups as follows: 1) The fist group includes patients who recover relatively quickly from their psychosis in any circumstance. In this group neuroleptics are not needed, perhaps even harmful in some cases, e.g. by binding the patient unnecessarily to the treatment system. 2) The second group consists of patients who require neuroleptics in all treatment circumstances to reach the best possible treatment outcome. 3) Between these two groups there is, however, a large group of patients who certainly benefit from neuroleptics, especially if other, mainly psychosocial, treatment methods are not available, but in whom the drug treatment very well can be replaced by intensive and extensive psychosocial interventions.
V. Lehtinen, J. Aaltonen, T. Koffert, V. Räkköläinen, E. SyvälahtiTwo-year outcome in first-episode psychosis treated according to an integrated model. Is immediate neuroleptisation always needed? Eur Psychiatry 2000 ; 15 : 312-20 In the experimental group (N=67) 42.9% of the patients did not receive neuroleptics at all during the whole two-year period, while the corresponding proportion in the control group (N=39) was 5.9%. The overall outcome of the whole group could be seen as rather favourable. The main result was that the outcome of the experimental group was equal or even somewhat better than that of the control group, also after controlling for age, gender and diagnosis. This indicates that an integrated approach, stressing intensive psychosocial measures, is recommended in the treatment of acute first-episode psychosis.
The psychological treatments used during the 2 year follow-up period by site, proportions by percentage. Mode of treatment Experiment Control Total P N = 67 N = 39 N = 106 Individual psychotherapy 25.4 28.2 26.4 0.750 Family therapy 67.2 38.5 56.6 0.004 Group therapy 4.5 15.4 8.5 0.052 Psychological treatment 73.1 53.9 66.0 0.043
API projektin 5 vuoden seuranta, Lehtinen K (2008) EG CG Ei neuroleptilääkitystä 37% 8% Jos käytetty, viikkoja 127 186 Ei sairaalahoitoa 2 5 v 88% 68% Eläkkeellä 27% 58%
Tarpeenmukainen hoito: Avoimen dialogin hoitojärjestelmän periaatteet (Aaltonen ym., 2011) Välittömän avun turvaaminen Verkostokeskeinen näkökulma Joustavuus ja liikkuvuus Vastuunoton turvaaminen ja saavutettavuus Psykologisen jatkuvuuden turvaaminen Epävarmuuden sieto prosessissa Dialogisuus
OPEN DIALOGUEM IN ACUTE PSYCHOSIS: VIIDEN VUODEN SEURANTA ENSIMMÄISTA KERTAA NON- AFFEKTIIVISEEN PSYKOOSIN SAIRASTUNEILLA POTILAILLA Seikkula et al. Psychotherapy Research, March 2006: 16(2),214-228 Aluksi osana valtakunnallista API (Akuutin Psykoosin Integroitu hoito) projektia Naturalistinen monikeskustutkimus: eri tutkimuskeskuksilla eri tehtävät API projektissa osa aloitti neuroleptilääkehoidon perinteisen hoitosuosituksen mukaisesti (n= 3 tutkimuskeskusta), osa pidättäytyi neuroleptilääkityksestä aktiivisen psykososiaalisen hoidon vaikutuksen arvioimiseksi. Anksiolyyttilääkitys tarvittaessa (n=3 tutkimuskeskusta) Aineisto (N=78) jaettu kahteen ryhmään: API ryhmä Länsi-Pohjasta: 1.4.-1992 31.12.1993 N = 33 ODAP ryhmä Länsi-Pohjasta 1.1.1994 31.3. 1997 N = 42 Kuvaava ei selittävä tutkimus
OPEN DIALOGUE IN ACUTE PSYCHOSIS 2 vuoden seuranta Taulukko 2. Psykoottisten oireiden määrä verrattuna neuroleptilääkitykseen 2 vuoden aikana/ % Oireiden määrä Neuroleptit 0 1 2 3 4 Yhteensä ------------------------------------- Ei käytetty 85 9 3 3 0 100 Käytetty tai jatkuu 58 17 8 17 0 100 ------------------------------------- Total 80 10 4 6 0 100
OPEN DIALOGUE IN ACUTE PSYCHOSIS Relapses compared to use of neuroleptics during the early phase of the treatment Neuroleptics Not-used Used Total/% Chi-sq. P -------------------------------------------------------- Relapses 0-2 years 0 56 7 63/ 82 8.97;3.030 At least 1 9 5 14/ 18 Relapses 2-5 years 0 47 9 56/ 73 2.96;2 ns At least 1 16 3 19 27 ---------------------------------------------------------- Total number of relapse cases 28%
5 vuoden seurantatulosten vertailu Länsi-Pohja vs. Tukholma ODAP Länsi-Pohja Tukholma* 1992-1997 N = 72 1991-1992 N=71 Diagnoosi: Skitsofrenia 59 % 54 % Muu non-affektiivinen psykoosi 41 % 46 % Keski-ikä naiset 26.5 30 miehet 27.5 29 Sairaalahoitopäivät 31 110 Neuroleptit 33 % 93 % - jatkuu 17 % 75 % GAF 66 55 Eläkkeellä 19 % 62 % *Svedberg, B., Mesterton, A. & Cullberg, J. (2001). First-episode non-affective psychosis in a total urban population: a 5-year follow-up. Social Psychiatry, 36:332-337.
Vertailu tavanomaiseen hoitoon Means of treatment process variables in three schizophrenia groups at the two-year follow up, t-test pair comparison Seikkula, J. et al. Ethical and Human Sciences and Services 2003, 5(3), 163-182. API ODAP Comparison group group group N=22 N=23 N=14 Hospitalization days Mean 35.9 14.3 116.9 ** SD 44.0 25.0 102.2 Number of family meetings Mean 26.1 20.1 8.9 *** SD 14.1 20.6 6.2
Frequencies of outcome variables in three schizophrenia groups at the two-year follow-up Seikkula, J. et al. Ethical and Human Sciences and Services 2003, 5(3), 163-182. API group ODAP Comparison group group group N=22 N=23 N=14 Number of relapsed 8 6 10 ** patients Employment status Studying or working 13 15 3 Unemployed 1 6 3 Disability allowance 8 2 8 *** Residual psychotic symptoms 0-1 14 19 7 ** 2-4 6 4 7
20 year follow-up of Open Dialogue in Western Lapland (Tomi Bergström et al, 2017) 65/ 99 were living all their life in Open Dialogue treatment area in Western Lapland More sever problems compared to those moved away 26% neuroleptic at start; 34% at the follow-up Mean 5 years, variation 2 to 8 years
Johtopäätöksiä Tutkimusten tulokset vaihtelevat sekä tutkimusasetelman että tutkimuksen seurannan pituuden mukaan Satunnaistetuissa kokeissa lyhyellä ajalla (6 12 kk), joissa psykoosilääkitys keskeytetty 6 vko 12 kk jälkeen, lääkityillä vähemmän uudelleen sairastumista, ja harvemmin palanneet työelämään Pitkällä seuranta-ajalla (2 7 v) ei lääkettä hoitoryhmällä parempi työtilanne ja sosiaalinen selviytyminen Kuolleisuuden ja neuroleptilääkityksen suhteesta saatu ristiriitaisia tuloksia. Observaatiotutkimuksessa validiteettiongelmia: Ei kontrolloitu tutkittujen potilaiden tausta yms. väliintulevia muuttujia, jolloin ei tiedetä mistäkorrelaatioihin perustuvat johtopäätökset tehdään.
Johtopäätöksiä Lääkityksen tarpeenmukainen hoito ei sinällään tuonut suurta hoidon tuloksen parannusta, mutta toisaalta auttoi sekä lääkityksen että sairaalahoidon vähentämiseen Erityisen hoito-ohjelman lisääminen (Soteria; Open Dialogue) tarpeenmukaiseen hoitoon edisti hoidon tulosta vähemmällä lääkehoidolla sekä psykoottisten oireiden vähenemisen, relapsien vähenemisen että työssä selviytymistä Psykososiaalisia hoito-ohjelmia on tutkittu todella vähän!
Onko vaihtoehtoja? Talking Back to Madness. Science,343, 2014
Psykoosin käypä hoito? Psykoosilääkkeiden teho positiivisten oireiden hoidossa ja uusien psykoosivaiheiden estossa on osoitettu vakuuttavasti kontrolloiduissa tutkimusasetelmissa Tämän selvityksen mukaan tutkimukset eivät osoita tätä. Useimmissa tutkimuksissa ei edes mitata positiivisia oireita ja relapsien määrä yhteydessä sekä psykoosilääkityksen keskeytykseen että seuranta-ajan lyhyyteen
Ellei ensipsykoosipotilaan skitsofreniadiagnoosi ole varma, lääkehoidon aloitusta voidaan siirtää 1 2 viikkoa, koska osa potilaista toipuu ilman psykoosilääkitystä. Skitsofreniapotilaiden lääkehoidon aloittamista heti ei ole perusteltu näissä tutkimuksissa ja muiden psykoottisten ongelmien hoidossa lääkehoidon aloittamista voitaisiin odottaa paljon pidempään kuin 1 2 vkoa
Loppusanat: J. Seikkula: Kuinka tutkimusasetelmat ja käytetyt tutkimusmenetelmät muokkaavat tuloksia psykoosihoidon tuloksellisuustutkimuksessa? Näyttöön perustuva psykoterapia, 2005:Seminaariesitys 12.-13.2. 2004 Tulosten vastakkaisuus pakottaa pohtimaan satunnaistettujen tutkimusten perusasetelmien aiheuttamaa ongelmaa itse hoitotilanteessa. Nämä tutkimuksethan toimivat koko ajan ryhmien keskiarvojen vertailuilla, jolloin merkitsevä ero saattaa syntyä siitä, että vain 20 30% ryhmästä saa kontrolliryhmästä poikkeavia arvoja. Tällä perusteella tehdään suositus, että kaikkiin potilaisiin pitäisi soveltaa kesiarvovertailujen osoittamaa menetelmää, vaikka suurin osa ryhmästä ei poikkea lainkaan koeryhmän tuloksesta. Ollaan lähellä vallankäyttöä, jossa hoitoa ei enää soviteta potilaan yksilöllisiin tarpeisiin, vaan nähdään yksilö keskiarvon edustajana. Duodecim Käypä hoito suosituksissa saattaa ilmaantua tämänkaltainen asenne. Joissakin kohdin lähteet merkitään huolimattomasti niin, että lähteet viittaavat aivan toisiin tutkimuksiin. Asioihin suhtaudutaan ikään kuin itsestäänselvyytenä, joita ei tarvitse huolellisesti perustella.
Taylor M, Cavanagh J, Hodgson R, Tiihonen J. Examining the effectiveness of antipsychotic medication in first-episode psychosis. J Psychopharmacol 2012; 26: 27 32. Leucht S, Tardy M, Komossa K, Heres S, Kissling W, Davis JM. Maintenance treatment with antipsychotic drugs for schizophrenia. Cochrane Database Syst Rev 2012; 5: CD008016. Harrow M, Jobe TH, Faull RN. Does treatment of schizophrenia with antipsychotic medications eliminate or reduce psychosis? A 20-year multifollow-up study. Psychol Med 2014; 44: 3007 16. Moilanen J, Haapea M, Miettunen J, Jaaskelainen E, Veijola J, Isohanni M, et al. Characteristics of subjects with schizophrenia spectrum disorder with and without antipsychotic medication a 10- year follow-up of the Northern Finland 1966 Birth Cohort study. Eur Psychiatry 2013; 28: 53 8. Wunderink, L., Nieboer, R.M., Wiersma, D., Sytema, S., Nienhuis, F.J., 2013. Recovery in remitted first-episode psychosis at 7 years of follow-up of an early dose reduction/ discontinuation or maintenance treatment strategy long-term follow-up of a 2-year randomized clinical trial