Comment
The active involvement of local leadership and stakeholder groups is crucial to sustain and develop programmes; mental health for all means all need to play a part. Therefore, as services are rolled out across low-income and middle-income countries, the global must engage with the local to forge an equal partnership to improve the lives of people with schizophrenia and their families. *Derrick Silove, Philip B Ward Psychiatry Research and Teaching Unit (DS) and Schizophrenia Research Unit (PBW), School of Psychiatry, University of New South Wales, Mental Health Centre, Liverpool Hospital, Sydney, NSW 2170, Australia [email protected]
4 5
6
7
8
9 10
We declare that we have no competing interests. Copyright @ Silove et al. Open Access article distributed under the terms of CC BY. 1 2 3
Prince M, Patel V, Saxena S, et al. No health without mental health. Lancet 2007; 370: 859–77. Collins PY, Patel V, Joestl SS, et al. Grand challenges in global mental health. Nature 2011; 475: 27–30. Gore F, Bloem P, Patton G. Global burden of disease in young people aged 10–24 years: a systematic analysis. Lancet 2011; 377: 2093–102.
11 12 13
Silove D, Ekblad S, Mollica R. The rights of the severely mentally ill in post-conflict societies. Lancet 2000; 355: 1548–49. Patel V, Kleinman A, Saraceno B. Protecting the rights of people with mental illness: a call to action for global mental health. In: Dudley M, Silove D, Gayle F, eds. Mental health and human rights. Oxford: Oxford University Press, 2012: 362–75. Chatterjee S, Naik S, John S, et al. Effectiveness of a community-based intervention for people with schizophrenia and their caregivers in India (COPSI): a randomised controlled trial. Lancet 2014; published online March 5. http://dx.doi.org/10.1016/S0140-6736(13)62629-X. WHO. Timor-Leste. In: Silove D, Tilman T, Hawkins Z, eds. Building back better: sustainable mental health care after emergencies. Geneva: World Health Organization, 2013: 83–88. Mitchell A, Davy V, Kim S, et al. Prevalence of metabolic syndrome and metabolic abnormalities in schizophrenia and related disorders—a systematic review and meta-analysis. Schizophr Bull 2013; 39: 306–18. Khandelwal S, Reddy K. Eliciting a policy response for the rising epidemic of overweight-obesity in India. Obes Rev 2013; 14: 114–25. Pérez-Iglesias R, Martínez-García O, Pardo-Garcia G, et al. Course of weight gain and metabolic abnormalities in first treated episode of psychosis: the first year is a critical period for development of cardiovascular risk factors. Int J Neuropsychopharmacol 2014; 17: 41–51. Wildgust H, Beary M. Are there modifiable risk factors which will reduce the excess mortality in schizophrenia? J Psychopharmacol 2010; 24: 37–50. Summerfield D. “Global mental health” is an oxymoron and medical imperialism. BMJ 2013; 346: f3509. Silove D, Bateman C, Brooks R, et al. Estimating clinically relevant mental disorders in a rural and an urban setting in postconflict Timor Leste. Arch Gen Psychiatry 2008; 65: 1205–12.
Wavebreak Media Ltd./Corbis
Cognitive therapy: at last an alternative to antipsychotics?
Published Online February 6, 2014 http://dx.doi.org/10.1016/ S0140-6736(13)62569-6 See Articles page 1395
1364
Schizophrenia causes substantial disability and premature mortality, and is one of the top causes of disease burden worldwide.1 Antipsychotic drugs revolutionised schizophrenia treatment when introduced in the 1950s, and numerous studies have shown that antipsychotics are effective for acute episodes, and as maintenance treatment, with a number needed to treat of 3 to prevent relapse.2 Evidence has also shown that some drugs could reduce mortality, mainly through a reduction in suicide rates.3 However, the clinical reality is that many patients stop taking antipsychotics for various reasons: sideeffects, absence of benefit, disorganisation, and because they do not perceive they have an illness. Although more than 20 different antipsychotics are in use for first-line treatment of schizophrenia, all essentially use the same mechanism, and drugs that use alternative mechanisms have yet to reach the market.4,5 Consequently, patients are faced with Hobson’s choice: antipsychotic treatment or nothing. This choice is further complicated because antipsychotics are associated with several distressing and potentially serious side-effects, including tardive dyskinesia, endocrine and sexual dysfunction, and cardiac dysrhythmia.6–9 Therefore, a viable treatment alternative is needed.
In The Lancet, Anthony Morrison and colleagues’ randomised trial10 provides ground-breaking evidence that cognitive therapy might be such an alternative. Cognitive therapy is a structured time-limited treatment that involves the therapist working collaboratively with the patient in weekly sessions over several months to reappraise psychotic experiences and modify unhelpful thought patterns and behaviours. Cognitive therapy is established as effective in treatment of schizophrenia, but in the past has always been used as an adjunct to antipsychotic treatment for patients with residual symptoms.11 Morrison and colleagues assessed the benefit of cognitive therapy for treatment of schizophrenia in patients who chose not to take antipsychotic drugs. The investigators randomly assigned 37 patients to cognitive therapy plus treatment as usual and 37 patients to treatment as usual alone, with a primary endpoint of total score on the Positive and Negative Syndrome Scale (PANSS). Patients received follow-up over at least 9 months. Cognitive therapy proved to be highly effective in reducing psychotic symptoms, and in improving function compared with treatment as usual; mean PANNS total scores were consistently lower in the cognitive therapy group than in the treatment as usual www.thelancet.com Vol 383 April 19, 2014
Comment
group, with an estimated between-group difference of −6·52 (95% CI −10·79 to −2·25). Cognitive therapy was well tolerated and had low dropout rates. These findings are impressive; however, some caution is warranted. First, the study did not have a placebo intervention. The potential effect of this limitation should not be underestimated because placebo effects can be large in schizophrenia trials,12 and have contributed to failed studies of new drug treatments for schizophrenia.13 The absence of placebo might be important in this trial because, although the assessors were masked to group allocation, patients were not, and the outcome measures rely on patient self-report. Although these measures are standard in schizophrenia trials, the risk of reporting biases might be large for cognitive therapy, because it explicitly focuses on the patient and therapist forming a close collaborative relationship. The potential effect of this bias is emphasised by evidence that effect sizes were 60% smaller in cognitive therapy trials that used singleblinded assessments than in those using unblinded assessments.11 The study by Morrison and colleagues did use masked assessments and showed that masking was largely achieved. Nevertheless, an issue remains regarding how to design double-blind trials of interventions such as cognitive therapy. The characteristics of the patients who entered the study should also be considered. The recruitment criteria specified that patients were engaged with a clinical team but had chosen not to take or had stopped antipsychotic treatment for at least 6 months. Furthermore, baseline symptom severity was relatively moderate, somewhat lower than that noted in patients typically entering acute drug trials13,14 for example, but nevertheless similar to levels noted in other outpatient treatment trials of schizophrenia.15,16 Also notable is that outcomes in the patient group as a whole, including those in the treatment as usual group, were relatively good. This result probably reflects the recruitment criteria, in particular that patients in hospital, who tend to have severe illnesses, were excluded. For these reasons, the study findings should not be generalised to all patients, particularly inpatients or patients not engaged with a clinical team. However, many patients could still be suitable for cognitive therapy. Finally, it could be argued, given the established efficacy of antipsychotic drugs, that the appropriate comparator intervention is antipsychotic treatment. However, because many patients choose not to take antipsychotic drugs, www.thelancet.com Vol 383 April 19, 2014
focus on these patients is useful to provide evidence for a group who are generally excluded from drug trials. Antipsychotic treatment was used at points during the course of Morrison and colleagues’ study in about a quarter of patients in both the cognitive therapy and treatment as usual groups. This treatment shows the way in which many patients use antipsychotic drugs—eg, taking them periodically during illness exacerbations— and might suggest that offering patients a choice supports their later engagement with antipsychotic treatment. Notwithstanding these caveats, Morrison and colleagues’ findings provide proof of concept that cognitive therapy is an alternative to antipsychotic treatment. Clearly this outcome will need further testing, but, if further work supports the relative effectiveness of cognitive therapy, a comparison between such therapy and antipsychotic treatment will be needed to inform patient choice. If positive, findings from such a comparison would be a step change in the treatment of schizophrenia, providing patients with a viable alternative to antipsychotic treatment for the first time, something that is sorely needed. Oliver Howes Clinical Sciences Centres and Institute of Psychiatry, London SE5 8AF, UK [email protected] I have received investigator-initiated research funding from, or participated in advisory or speaker meetings organised by, several manufacturers of antipsychotics: AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Janssen, Lyden-Delta, Servier, and Roche, and have provided cognitive therapy to patients as part of UK National Health Service treatment. 1 2
3
4
5
6 7
8
9
Van Os J, Kapur S. Schizophrenia. Lancet 2009; 374: 635–45. Leucht S, Tardy M, Komossa K, et al. Antipsychotic drugs versus placebo for relapse prevention in schizophrenia: a systematic review and meta-analysis. Lancet 2012; 379: 2063–71. Tiihonen J, Lonnqvist J, Wahlbeck K, et al. 11-year follow-up of mortality in patients with schizophrenia: a population-based cohort study (FIN11 study). Lancet 2009; 374: 620–27. Howes OD, Egerton A, Allan V, McGuire P, Stokes P, Kapur S. Mechanisms underlying psychosis and antipsychotic treatment response in schizophrenia: insights from PET and SPECT imaging. Curr Pharm Des 2009; 15: 2550–59. Howes OD, Kambeitz J, Kim E, et al. The nature of dopamine dysfunction in schizophrenia and what this means for treatment. Arch Gen Psychiatry 2012; 69: 776–86. Taylor D. Psychopharmacology and adverse effects of antipsychotic long-acting injections: a review. Br J Psychiatry 2009; 52: S13–19. Howes OD, Wheeler MJ, Meaney AM, et al. Bone mineral density and its relationship to prolactin levels in patients taking antipsychotic treatment. J Clin Psychopharmacol 2005; 25: 259–61. Leucht S, Cipriani A, Spineli L, et al. Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: a multiple-treatments meta-analysis. Lancet 2013; 382: 951–62. Howes OD, Wheeler MJ, Pilowsky LS, Landau S, Murray RM, Smith S. Sexual function and gonadal hormones in patients taking antipsychotic treatment for schizophrenia or schizoaffective disorder. J Clin Psychiatry 2007; 68: 361–67.
1365
Comment
10
11
12
13
Morrison AP, Turkington D, Pyle M, et al. Cognitive therapy for people with schizophrenia spectrum disorders not taking antipsychotic drugs: a single-blind randomised controlled trial. Lancet 2014; published online Feb 6. http://dx.doi.org/10.1016/S0140-6736(13)62246-1. Wykes T, Steel C, Everitt B, Tarrier N. Cognitive behavior therapy for schizophrenia: effect sizes, clinical models, and methodological rigor. Schizophr Bull 2008; 34: 523–37. Khin NA, Chen YF, Yang Y, Yang P, Laughren TP. Exploratory analyses of efficacy data from schizophrenia trials in support of new drug applications submitted to the US Food and Drug Administration. J Clin Psychiatry 2012; 73: 856–64. Kinon BJ, Zhang L, Millen BA, et al. A multicenter, inpatient, phase 2, doubleblind, placebo-controlled dose-ranging study of LY2140023 monohydrate in patients with DSM-IV schizophrenia. J Clin Psychopharmacol 2011; 31: 349–55.
14
15
16
Ogasa M, Kimura T, Nakamura M, Guarino J. Lurasidone in the treatment of schizophrenia: a 6-week, placebo-controlled study. Psychopharmacology 2013; 225: 519–30. Jones PB, Barnes TR, Davies L, et al. Randomized controlled trial of the effect on quality of life of second- vs first-generation antipsychotic drugs in schizophrenia: Cost Utility of the Latest Antipsychotic Drugs in Schizophrenia Study (CUtLASS 1). Arch Gen Psychiatry 2006; 63: 1079–87. Lieberman JA, Stroup TS, McEvoy JP, et al. Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. N Engl J Med 2005; 353: 1209–23.
Jim Varney/Science Photo Library
Common adolescent mental disorders: transition to adulthood
Published Online January 16, 2014 http://dx.doi.org/10.1016/ S0140-6736(13)62633-1 See Articles page 1404
1366
Mental disorders are common, although reported rates differ according to developmental stage.1 The prevalence of common mental disorders such as depression increases in adolescence,1,2 and many people will experience such a disorder by young adulthood.3 Mental disorder in adolescence increases the risk of later adult disorder,4–6 and adults with mental disorder often have their first episode in adolescence.1,7 Therefore, adolescence is potentially an important time for mental health interventions to reduce both present and long-term impairment. However, there is little detailed knowledge about the prognosis of common adolescent mental disorders during the transition to adulthood. A greater understanding of the course and prognosis of adolescent-onset common mental disorders is needed to identify those at highest risk of later problems, to inform decisions about when to intervene, and to help allocate clinical resources efficiently. The prospective longitudinal cohort study by George Patton and colleagues8 in The Lancet is important because it addresses this knowledge gap. The investigators aimed to assess how often depression and anxiety persist from adolescence to adulthood, and to identify which demographic, behavioural, and disorder characteristics predict such persistence. A large community sample of adolescents was followed up at several timepoints over a 14-year period, from mid-adolescence into their late 20s, allowing a detailed assessment of the transition through adolescence into adulthood. The results confirm that depression and anxiety are common during adolescence (affecting 29% [95% CI 25–32] of boys and 54% [51–57] of girls), and that adolescent disorders predict young adulthood disorder—almost 60% of participants who had an episode during adolescence reported a further episode as a young adult. The investigators also report that, by the late 20s, the prevalence of disorder had decreased
(odds ratio [OR] 0·57, 95% CI 0·45–0·73). Many of the participants who had an adolescent episode did not go on to have a further episode as a young adult. Adolescence is a transitional stage in development characterised by complex psychosocial, neurobiological, and brain circuitry changes.9 However, further work is needed to understand how the interactions between biology and the environment affect adolescent psychopathology. What is reassuring from Patton and colleagues’ study is that the rates of common mental disorders in the general population seem to decrease when adulthood is reached. These results are consistent with previous studies that have shown the prevalence of common mental disorders decelerating into adulthood,7 and a decrease in depressive symptoms from late adolescence into early adulthood.10 However, several factors should be considered in the interpretation of these results. First, Patton and colleagues’ study focused on the course and prognosis of depression and anxiety. Although these mental disorders are the most prevalent in this age group, other psychiatric disorders are relevant too. Adult disorders are often preceded by the same diagnosis in adolescence (homotypic continuity), but they might also be followed or preceded by a different disorder (heterotypic continuity). For example, the Dunedin Longitudinal Study2 showed that adult anxiety disorders were preceded by a range of juvenile disorders, and the Great Smoky Mountains Study11 showed heterotypic continuity from depression to anxiety, anxiety to depression, attention-deficit hyperactivity disorder to oppositional defiant disorder, and from anxiety and conduct disorder to substance misuse. To account for anxiety and depression alone could underestimate continued difficulties from adolescence www.thelancet.com Vol 383 April 19, 2014
The active involvement of local leadership and stakeholder groups is crucial to sustain and develop programmes; mental health for all means all need to play a part. Therefore, as services are rolled out across low-income and middle-income countries, the global must engage with the local to forge an equal partnership to improve the lives of people with schizophrenia and their families. *Derrick Silove, Philip B Ward Psychiatry Research and Teaching Unit (DS) and Schizophrenia Research Unit (PBW), School of Psychiatry, University of New South Wales, Mental Health Centre, Liverpool Hospital, Sydney, NSW 2170, Australia [email protected]
4 5
6
7
8
9 10
We declare that we have no competing interests. Copyright @ Silove et al. Open Access article distributed under the terms of CC BY. 1 2 3
Prince M, Patel V, Saxena S, et al. No health without mental health. Lancet 2007; 370: 859–77. Collins PY, Patel V, Joestl SS, et al. Grand challenges in global mental health. Nature 2011; 475: 27–30. Gore F, Bloem P, Patton G. Global burden of disease in young people aged 10–24 years: a systematic analysis. Lancet 2011; 377: 2093–102.
11 12 13
Silove D, Ekblad S, Mollica R. The rights of the severely mentally ill in post-conflict societies. Lancet 2000; 355: 1548–49. Patel V, Kleinman A, Saraceno B. Protecting the rights of people with mental illness: a call to action for global mental health. In: Dudley M, Silove D, Gayle F, eds. Mental health and human rights. Oxford: Oxford University Press, 2012: 362–75. Chatterjee S, Naik S, John S, et al. Effectiveness of a community-based intervention for people with schizophrenia and their caregivers in India (COPSI): a randomised controlled trial. Lancet 2014; published online March 5. http://dx.doi.org/10.1016/S0140-6736(13)62629-X. WHO. Timor-Leste. In: Silove D, Tilman T, Hawkins Z, eds. Building back better: sustainable mental health care after emergencies. Geneva: World Health Organization, 2013: 83–88. Mitchell A, Davy V, Kim S, et al. Prevalence of metabolic syndrome and metabolic abnormalities in schizophrenia and related disorders—a systematic review and meta-analysis. Schizophr Bull 2013; 39: 306–18. Khandelwal S, Reddy K. Eliciting a policy response for the rising epidemic of overweight-obesity in India. Obes Rev 2013; 14: 114–25. Pérez-Iglesias R, Martínez-García O, Pardo-Garcia G, et al. Course of weight gain and metabolic abnormalities in first treated episode of psychosis: the first year is a critical period for development of cardiovascular risk factors. Int J Neuropsychopharmacol 2014; 17: 41–51. Wildgust H, Beary M. Are there modifiable risk factors which will reduce the excess mortality in schizophrenia? J Psychopharmacol 2010; 24: 37–50. Summerfield D. “Global mental health” is an oxymoron and medical imperialism. BMJ 2013; 346: f3509. Silove D, Bateman C, Brooks R, et al. Estimating clinically relevant mental disorders in a rural and an urban setting in postconflict Timor Leste. Arch Gen Psychiatry 2008; 65: 1205–12.
Wavebreak Media Ltd./Corbis
Cognitive therapy: at last an alternative to antipsychotics?
Published Online February 6, 2014 http://dx.doi.org/10.1016/ S0140-6736(13)62569-6 See Articles page 1395
1364
Schizophrenia causes substantial disability and premature mortality, and is one of the top causes of disease burden worldwide.1 Antipsychotic drugs revolutionised schizophrenia treatment when introduced in the 1950s, and numerous studies have shown that antipsychotics are effective for acute episodes, and as maintenance treatment, with a number needed to treat of 3 to prevent relapse.2 Evidence has also shown that some drugs could reduce mortality, mainly through a reduction in suicide rates.3 However, the clinical reality is that many patients stop taking antipsychotics for various reasons: sideeffects, absence of benefit, disorganisation, and because they do not perceive they have an illness. Although more than 20 different antipsychotics are in use for first-line treatment of schizophrenia, all essentially use the same mechanism, and drugs that use alternative mechanisms have yet to reach the market.4,5 Consequently, patients are faced with Hobson’s choice: antipsychotic treatment or nothing. This choice is further complicated because antipsychotics are associated with several distressing and potentially serious side-effects, including tardive dyskinesia, endocrine and sexual dysfunction, and cardiac dysrhythmia.6–9 Therefore, a viable treatment alternative is needed.
In The Lancet, Anthony Morrison and colleagues’ randomised trial10 provides ground-breaking evidence that cognitive therapy might be such an alternative. Cognitive therapy is a structured time-limited treatment that involves the therapist working collaboratively with the patient in weekly sessions over several months to reappraise psychotic experiences and modify unhelpful thought patterns and behaviours. Cognitive therapy is established as effective in treatment of schizophrenia, but in the past has always been used as an adjunct to antipsychotic treatment for patients with residual symptoms.11 Morrison and colleagues assessed the benefit of cognitive therapy for treatment of schizophrenia in patients who chose not to take antipsychotic drugs. The investigators randomly assigned 37 patients to cognitive therapy plus treatment as usual and 37 patients to treatment as usual alone, with a primary endpoint of total score on the Positive and Negative Syndrome Scale (PANSS). Patients received follow-up over at least 9 months. Cognitive therapy proved to be highly effective in reducing psychotic symptoms, and in improving function compared with treatment as usual; mean PANNS total scores were consistently lower in the cognitive therapy group than in the treatment as usual www.thelancet.com Vol 383 April 19, 2014
Comment
group, with an estimated between-group difference of −6·52 (95% CI −10·79 to −2·25). Cognitive therapy was well tolerated and had low dropout rates. These findings are impressive; however, some caution is warranted. First, the study did not have a placebo intervention. The potential effect of this limitation should not be underestimated because placebo effects can be large in schizophrenia trials,12 and have contributed to failed studies of new drug treatments for schizophrenia.13 The absence of placebo might be important in this trial because, although the assessors were masked to group allocation, patients were not, and the outcome measures rely on patient self-report. Although these measures are standard in schizophrenia trials, the risk of reporting biases might be large for cognitive therapy, because it explicitly focuses on the patient and therapist forming a close collaborative relationship. The potential effect of this bias is emphasised by evidence that effect sizes were 60% smaller in cognitive therapy trials that used singleblinded assessments than in those using unblinded assessments.11 The study by Morrison and colleagues did use masked assessments and showed that masking was largely achieved. Nevertheless, an issue remains regarding how to design double-blind trials of interventions such as cognitive therapy. The characteristics of the patients who entered the study should also be considered. The recruitment criteria specified that patients were engaged with a clinical team but had chosen not to take or had stopped antipsychotic treatment for at least 6 months. Furthermore, baseline symptom severity was relatively moderate, somewhat lower than that noted in patients typically entering acute drug trials13,14 for example, but nevertheless similar to levels noted in other outpatient treatment trials of schizophrenia.15,16 Also notable is that outcomes in the patient group as a whole, including those in the treatment as usual group, were relatively good. This result probably reflects the recruitment criteria, in particular that patients in hospital, who tend to have severe illnesses, were excluded. For these reasons, the study findings should not be generalised to all patients, particularly inpatients or patients not engaged with a clinical team. However, many patients could still be suitable for cognitive therapy. Finally, it could be argued, given the established efficacy of antipsychotic drugs, that the appropriate comparator intervention is antipsychotic treatment. However, because many patients choose not to take antipsychotic drugs, www.thelancet.com Vol 383 April 19, 2014
focus on these patients is useful to provide evidence for a group who are generally excluded from drug trials. Antipsychotic treatment was used at points during the course of Morrison and colleagues’ study in about a quarter of patients in both the cognitive therapy and treatment as usual groups. This treatment shows the way in which many patients use antipsychotic drugs—eg, taking them periodically during illness exacerbations— and might suggest that offering patients a choice supports their later engagement with antipsychotic treatment. Notwithstanding these caveats, Morrison and colleagues’ findings provide proof of concept that cognitive therapy is an alternative to antipsychotic treatment. Clearly this outcome will need further testing, but, if further work supports the relative effectiveness of cognitive therapy, a comparison between such therapy and antipsychotic treatment will be needed to inform patient choice. If positive, findings from such a comparison would be a step change in the treatment of schizophrenia, providing patients with a viable alternative to antipsychotic treatment for the first time, something that is sorely needed. Oliver Howes Clinical Sciences Centres and Institute of Psychiatry, London SE5 8AF, UK [email protected] I have received investigator-initiated research funding from, or participated in advisory or speaker meetings organised by, several manufacturers of antipsychotics: AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Janssen, Lyden-Delta, Servier, and Roche, and have provided cognitive therapy to patients as part of UK National Health Service treatment. 1 2
3
4
5
6 7
8
9
Van Os J, Kapur S. Schizophrenia. Lancet 2009; 374: 635–45. Leucht S, Tardy M, Komossa K, et al. Antipsychotic drugs versus placebo for relapse prevention in schizophrenia: a systematic review and meta-analysis. Lancet 2012; 379: 2063–71. Tiihonen J, Lonnqvist J, Wahlbeck K, et al. 11-year follow-up of mortality in patients with schizophrenia: a population-based cohort study (FIN11 study). Lancet 2009; 374: 620–27. Howes OD, Egerton A, Allan V, McGuire P, Stokes P, Kapur S. Mechanisms underlying psychosis and antipsychotic treatment response in schizophrenia: insights from PET and SPECT imaging. Curr Pharm Des 2009; 15: 2550–59. Howes OD, Kambeitz J, Kim E, et al. The nature of dopamine dysfunction in schizophrenia and what this means for treatment. Arch Gen Psychiatry 2012; 69: 776–86. Taylor D. Psychopharmacology and adverse effects of antipsychotic long-acting injections: a review. Br J Psychiatry 2009; 52: S13–19. Howes OD, Wheeler MJ, Meaney AM, et al. Bone mineral density and its relationship to prolactin levels in patients taking antipsychotic treatment. J Clin Psychopharmacol 2005; 25: 259–61. Leucht S, Cipriani A, Spineli L, et al. Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: a multiple-treatments meta-analysis. Lancet 2013; 382: 951–62. Howes OD, Wheeler MJ, Pilowsky LS, Landau S, Murray RM, Smith S. Sexual function and gonadal hormones in patients taking antipsychotic treatment for schizophrenia or schizoaffective disorder. J Clin Psychiatry 2007; 68: 361–67.
1365
Comment
10
11
12
13
Morrison AP, Turkington D, Pyle M, et al. Cognitive therapy for people with schizophrenia spectrum disorders not taking antipsychotic drugs: a single-blind randomised controlled trial. Lancet 2014; published online Feb 6. http://dx.doi.org/10.1016/S0140-6736(13)62246-1. Wykes T, Steel C, Everitt B, Tarrier N. Cognitive behavior therapy for schizophrenia: effect sizes, clinical models, and methodological rigor. Schizophr Bull 2008; 34: 523–37. Khin NA, Chen YF, Yang Y, Yang P, Laughren TP. Exploratory analyses of efficacy data from schizophrenia trials in support of new drug applications submitted to the US Food and Drug Administration. J Clin Psychiatry 2012; 73: 856–64. Kinon BJ, Zhang L, Millen BA, et al. A multicenter, inpatient, phase 2, doubleblind, placebo-controlled dose-ranging study of LY2140023 monohydrate in patients with DSM-IV schizophrenia. J Clin Psychopharmacol 2011; 31: 349–55.
14
15
16
Ogasa M, Kimura T, Nakamura M, Guarino J. Lurasidone in the treatment of schizophrenia: a 6-week, placebo-controlled study. Psychopharmacology 2013; 225: 519–30. Jones PB, Barnes TR, Davies L, et al. Randomized controlled trial of the effect on quality of life of second- vs first-generation antipsychotic drugs in schizophrenia: Cost Utility of the Latest Antipsychotic Drugs in Schizophrenia Study (CUtLASS 1). Arch Gen Psychiatry 2006; 63: 1079–87. Lieberman JA, Stroup TS, McEvoy JP, et al. Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. N Engl J Med 2005; 353: 1209–23.
Jim Varney/Science Photo Library
Common adolescent mental disorders: transition to adulthood
Published Online January 16, 2014 http://dx.doi.org/10.1016/ S0140-6736(13)62633-1 See Articles page 1404
1366
Mental disorders are common, although reported rates differ according to developmental stage.1 The prevalence of common mental disorders such as depression increases in adolescence,1,2 and many people will experience such a disorder by young adulthood.3 Mental disorder in adolescence increases the risk of later adult disorder,4–6 and adults with mental disorder often have their first episode in adolescence.1,7 Therefore, adolescence is potentially an important time for mental health interventions to reduce both present and long-term impairment. However, there is little detailed knowledge about the prognosis of common adolescent mental disorders during the transition to adulthood. A greater understanding of the course and prognosis of adolescent-onset common mental disorders is needed to identify those at highest risk of later problems, to inform decisions about when to intervene, and to help allocate clinical resources efficiently. The prospective longitudinal cohort study by George Patton and colleagues8 in The Lancet is important because it addresses this knowledge gap. The investigators aimed to assess how often depression and anxiety persist from adolescence to adulthood, and to identify which demographic, behavioural, and disorder characteristics predict such persistence. A large community sample of adolescents was followed up at several timepoints over a 14-year period, from mid-adolescence into their late 20s, allowing a detailed assessment of the transition through adolescence into adulthood. The results confirm that depression and anxiety are common during adolescence (affecting 29% [95% CI 25–32] of boys and 54% [51–57] of girls), and that adolescent disorders predict young adulthood disorder—almost 60% of participants who had an episode during adolescence reported a further episode as a young adult. The investigators also report that, by the late 20s, the prevalence of disorder had decreased
(odds ratio [OR] 0·57, 95% CI 0·45–0·73). Many of the participants who had an adolescent episode did not go on to have a further episode as a young adult. Adolescence is a transitional stage in development characterised by complex psychosocial, neurobiological, and brain circuitry changes.9 However, further work is needed to understand how the interactions between biology and the environment affect adolescent psychopathology. What is reassuring from Patton and colleagues’ study is that the rates of common mental disorders in the general population seem to decrease when adulthood is reached. These results are consistent with previous studies that have shown the prevalence of common mental disorders decelerating into adulthood,7 and a decrease in depressive symptoms from late adolescence into early adulthood.10 However, several factors should be considered in the interpretation of these results. First, Patton and colleagues’ study focused on the course and prognosis of depression and anxiety. Although these mental disorders are the most prevalent in this age group, other psychiatric disorders are relevant too. Adult disorders are often preceded by the same diagnosis in adolescence (homotypic continuity), but they might also be followed or preceded by a different disorder (heterotypic continuity). For example, the Dunedin Longitudinal Study2 showed that adult anxiety disorders were preceded by a range of juvenile disorders, and the Great Smoky Mountains Study11 showed heterotypic continuity from depression to anxiety, anxiety to depression, attention-deficit hyperactivity disorder to oppositional defiant disorder, and from anxiety and conduct disorder to substance misuse. To account for anxiety and depression alone could underestimate continued difficulties from adolescence www.thelancet.com Vol 383 April 19, 2014
