Antidepressants and Suicide (1) Christian Jonathan Haverkampf – psychiatry series

Antidepressants-and-Suicide-1-Christian-Jonathan-Haverkampf-psychiatry-series

ANtidepressants and Suicide

Dr Christian Jonathan Haverkampf M.D.

Antidepressants can be helpful in preventing the suicide of a depressed person in clinical practice, but there is also a discussion about whether antidepressants can raise the risk of suicide in certain situations.

Keywords: suicide, antidepressants, medication, psychiatry, psychotherapy, communication, medicine

Contents

Introduction. 3

Causation. 3

Children and Adolescents. 4

Children. 4

Adolescents. 4

Are all Antidepressants Equal?. 4

Non-SSRIs. 5

Inclusion Criteria. 5

Motivation. 5

Reasons. 6

Research Problems. 6

Confounding. 6

Sponsored Studies. 7

Age. 7

Risk-Benefit Ratio. 7

Monitoring. 8

A Better Understanding. 8

References. 10

Introduction

Prescribing of antidepressants has increased greatly over them last decades. This increase has coincided with a fall in rates of suicide, leading some researchers to suggest a causal association. As depression is the main psychiatric condition leading to suicide, it seems reasonable to infer that rises in antidepressant prescribing, which indicate improved management of depression, should have a beneficial effect on suicide rates. Indeed, an intervention to improve general practitioners’ management of depression in a Swedish community resulted in increased antidepressant prescribing and a short-term reduction in suicide. However, one also needs to bear in mind that the effectiveness of antidepressants in childhood and adolescence is less clear than in adults.

However, there is a concern that antidepressants may precipitate suicidal behavior. In October 2004, the US Food and Drug Administration issued an advisory that antidepressants may be associated with an increased risk of suicidal thoughts and behaviors in children and adolescents. These warnings were prompted by a meta-analysis of all available randomized trials of antidepressants in this age group, in which patients randomized to antidepressants had nearly twice the rate of suicidal ideation or behavior relative to those given placebo. These concerns prompted the US Food and Drug Administration to undertake a reanalysis of all its available antidepressant trials in adults as well. This meta-analysis and several subsequent analyses of short-term trials found no increased risk of suicidality in adult antidepressant users. However, the situation seems to be different for children and possibly adolescents.

Causation

Despite the widespread use of antidepressant medications, particularly selective serotonin reuptake inhibitors (SSRIs), there is inconsistent evidence that growth in antidepressant use has reduced the prevalence of suicidal ideation or suicide attempts during the past decades. (Haverkampf, 2018a) Nonrandomized studies comparing users of different antidepressant classes, including SSRIs, tricyclic agents (TCAs), serotonin-norepinephrine reuptake inhibitors and other drugs, have reported small or no differences in suicides and suicide attempts. However, serious questions remain whether these studies had adequate statistical power or were adequately controlled for prescribing biases caused by preferential avoidance of TCAs in patients at high risk. Since suicidal thoughts and behaviors do not happen in a vacuum, there are many aspects most studies on suicidal behavior may not account for, which can, however, be highly relevant. Internal and externa communication seems to play a more fundamental role in suicidal ideation, which is also affected by medication, but not solely by it.

Children and Adolescents

An increased risk of suicidal behavior has been reported in children and adolescents. It is possible that an increased short-term risk may be counterbalanced by a longer-term reduction in suicidal behavior. Another explanation given has been that patients on SSRIs may be more open about how they feel.

Time trends for suicide and non-fatal self-harm in children and adolescents have not provided consistent evidence of adverse trends paralleling increased prescribing in the 1990s, although there is some evidence of a rise in non-fatal self-harm in young females. Furthermore, in the United States, research suggests that patients in their teens, the age group with the largest increase in antidepressant use, experienced the greatest falls in suicide.

Children

There is no strong evidence that increases in antidepressant prescribing lie behind recent reductions in population suicides. Furthermore, data from pediatric trials suggest that SSRIs are associated with an increased risk of suicidal behavior and most SSRIs seem to be ineffective for childhood depression. However, current concerns about the safety of SSRIs come from clinical trials both of too short duration (< 10 weeks) to identify longer term beneficial effects and are carried out in children and adolescents, among whom suicide is rare.

Adolescents

A US Food and Drug Administration advisory has warned that antidepressants may be associated with an increased risk of suicidal thoughts and behaviors in adolescents. This prompted a meta-analysis of trials in adults that found no overall increase in risk, but individual agents could not be studied. A later study concluded that there were equal event rates across antidepressant agents. A review of evidence from pediatric trials by the Committee on Safety of Medicines in Britain led to most selective serotonin re-uptake inhibitors (SSRIs) being contraindicated in patients younger than eighteen.

Are all Antidepressants Equal?

There has been the theory that the less activating antidepressants, that is the SSRIs rather than the SNRIs, may be a safer choice if there is a risk of activating suicidal thoughts. However, there is not much empirical data to support this.

Several observational studies have reported small or no differences in suicides and suicide attempts between antidepressant classes and a meta-analysis of randomized controlled trial data that found no difference in suicide attempt rates between SSRI and TCA users. Similar to a cohort study using General Practice Research Database data, they found a higher rate of suicidal acts in venlafaxine users compared with SSRI users, even after adjustment for measured confounders. This effect was attenuated in secondary analyses restricted to treatment-naive users, suggesting some residual confounding in our primary analysis. In contrast to a case-control study in Ontario residents aged 66 years and older, they did not observe an increased risk of violent suicide among SSRI initiators relative to initiators of other antidepressants.

Non-SSRIs

A nested case-control study in residents of Ontario, Canada, aged 66 years and older found that SSRIs were associated with a nearly 5-fold increased risk of suicide during the first month of treatment compared with other antidepressants, but it found no difference between classes during subsequent periods. The investigators also observed a higher risk of violent suicide among SSRI users. However, a study using postmortem data found that a lower proportion of suicides was violent among SSRI users than among non–antidepressant users.

Inclusion Criteria

The inclusion criteria and the factors controlled for seem to play an important role. For example, studies have documented that venlafaxine tends to be prescribed to people with past SSRI treatment failure and with a greater burden of suicide risk factors, which needs to be controlled for. In one study, the differences between citalopram and fluoxetine were attenuated when the population was restricted to subjects with no antidepressant use in the 3 years prior to antidepressant initiation. In the same study, the higher risk of venlafaxine was attenuated when the population was restricted to subjects with no antidepressant use in the 3 years prior to antidepressant initiation. However, citalopram was linked less to violent suicide attempts, even when restricting treatment to treatment-naïve subjects and no suicide attempts for the previous three years.

In a study of a population of 287 543 adults aged 18 years and older initiating antidepressant therapy in British Columbia between January 1, 1997, and December 31, 2005, the researchers observed no clinically meaningful variation in the risk of suicide and suicide attempt by the type of antidepressant initiated. Effect sizes became more similar after restriction to subjects without any antidepressant use in the past 3 years, a population which is probably much closer to a population of first-time antidepressant users and an analysis within this population is less confounded by prior treatment experience and progression of the underlying condition, providing a more valid estimate of the causal treatment effects.

Motivation

Suicide is rare, even among people with depression. Thus, most clinical trials have insufficient power to provide clear evidence on the effect of antidepressants on suicide. Since suicidal ideation and behavior is multifactorial looking only at a possible direct effect of the antidepressant rather than at how this effect may interact with other factors and their effects can be misleading. Besides psychological intrapersonal factors and the effect of a different mood on interpersonal communication, external factors, such as the available means to commit suicide can play a role.

Since motivation is a product of applying one’s internal basic parameters, such as needs, values and aspirations to the world, it requires the ability to read this information. If survival as a need and continued life as a value and aspiration are very basic to our existence, a motivation to commit suicide must mean that information is either not read or read incorrectly. Most mental health conditions have an effect of internal communication patterns (Haverkampf, 2010b, 2010a, 2017a, 2018b), which can also change the information which is available about oneself. By ameliorating the condition and its effects, antidepressant medication can so also prevent suicidal ideation and behavior.

Reasons

An important question which is often left unanswered is why an individual commits suicide, this ultimate aggressive act turned against oneself. Medication can lower certain symptoms of depression but it cannot directly address a complex thought process. (Haverkampf, 2010a, 2018d, 2018c) Many different factors should to be addressed in therapy, but paramount about them is how a person communicates with himself or herself and with others. Distortions in communication systems are quite often a reason that leads to misperceptions, misattributions and unhelpful thought patterns.

Research Problems

Most population studies have concluded that recent rises in prescribing have contributed to falls in suicides, although there are exceptions. Interpretation of the findings is not straightforward. As mentioned above, several factors usually need to fall in place that an individual contemplates suicide. Also, a range of factors can influence population suicide rates. It is therefore challenging to distinguish the discrete effects of increased antidepressant prescribing from changes in other risk factors.

Confounding

Confounding occurs if, for example, certain antidepressants were more likely to be given to patients with a greater background risk of suicide. This makes it necessary to control for sociodemographic, clinical, and health care utilization factors likely to be independent predictors of suicidality using traditional multivariate and high-dimensional propensity score techniques. The ability to fully adjust for mental health status is frequently limited by the measurement and reporting of mental health conditions as ICD-10 diagnoses.

Well-validated behavioral risk factors such as impulsivity and hopelessness, environmental factors such as access to lethal means, and family history of completed suicide would not be measured in claims data. Random misclassification of confounders in health care utilization databases leads to incomplete adjustment of confounding bias.

While underreporting of suicide deaths is likely nondifferential, there is a possibility that patients treated with specific agents or having specific histories might attract closer scrutiny for potential suicide. Patients using TCAs, which are known to be fatal in overdose, might be more likely to receive a suicide diagnosis.

Sponsored Studies

Soon after the launch of fluoxetine a series of reports were published suggesting worsening of depression and emergence of suicidal thoughts in some people. The discussion became more heated after a review of data from pediatric trials of SSRIs suggested that published findings present a more favorable risk-benefit profile than unpublished trials sponsored by industry. It is true that many studies in this area have been supported by the pharmaceutical industry, which in itself is not necessarily bad, but it has probably contributed to the intensity of the discussion.

Age

Furthermore, declining overall suicide trends may mask rises in some age and sex groups. In Australia, rises in antidepressant prescribing were associated with falls in suicide among some age and sex groups but increases in others.

There are two reasons why an adverse effect of antidepressants on suicide risk may have been overlooked in adult clinical trials. Self-harm is fortunately still relatively rare, and most clinical trials lack power to detect any increased risk. Also, the possibility may not have been specifically investigated in the clinical trials. The increased risk in children may have been detected either because of the increased prevalence of suicidal thoughts and self-harm in young people (giving greater power) or because the absence of beneficial effects meant that adverse effects dominated the clinical picture.

Risk-Benefit Ratio

From the population perspective, the balance sheet of risks and benefits of SSRIs is unclear. Any antidepressant induced suicides are probably offset by the beneficial effects of antidepressants on depression and long-term suicide risk associated with untreated depression. The low toxicity of SSRIs in overdose will have prevented some suicides. The balance of risks and benefits may vary depending on an individual’s underlying suicide risk. For patients with conditions that have a high risk of suicide, such as severe depression, the risk-benefit balance may be more favorable than for patients with conditions such as anxiety and mild depression, in which suicide is rare. It is in these lower risk conditions, however, that much of the recent rise in prescribing has probably occurred.

Depression is a common and disabling condition, and so the safety of drugs used in its management is crucial. Future trials of antidepressants should be of sufficient duration to detect longer term benefits of this class of drug and balance these against possible risks. They should also systematically collect data on suicidal thoughts and behavior. Long term studies are required to assess the effect on population health of recent rises in antidepressant prescribing.

Monitoring

Treatment decisions should be based on efficacy, and clinicians should be vigilant in monitoring after initiating therapy with any antidepressant agent. SSRIs are often the preferred choice in adults. Overdoses of antidepressants are still a common means of suicide because of their availability to the patient. Tricyclic antidepressants are considerably more toxic in overdose than SSRIs. Consequently, a switch from tricyclics to SSRIs as first line treatment for depression could prevent a significant number of overdose deaths a year. However, medication switches seem rare in clinical practice. As the rate of antidepressant prescribing has increased in general, the prescribing of SSRIs has increased, but the number of patients on TCAs has not decreased by much.

A Better Understanding

However, equally important is to understand why suicides occur. The motivation behind a suicide may be due to a mix of several factors. As mentioned, CFT works with internal and external communication patterns to work out individual needs, values and aspirations in the short and long run, while paying attention to any concurrent psychiatric conditions. It is important to realize that suicidal thinking and behavior is usually not solely due to changes in mood or other psychiatric parameters. (Haverkampf, 2012a, 2012b, 2017b)


Dr Jonathan Haverkampf, M.D. MLA (Harvard) LL.M. trained in medicine, psychiatry and psychotherapy and works in private practice for psychotherapy, counselling and psychiatric medication in Dublin, Ireland. He also has advanced degrees in management and law. The author can be reached by email at jo****************@gm***.com or on the websites www.jonathanhaverkampf.ie and www.jonathanhaverkampf.com.

References

Baldessarini  RJTondo  LStrombom  IMDominguez  SFawcett  JLicinio  JOquendo  MATollefson  GDValuck  RJTohen  M Ecological studies of antidepressant treatment and suicidal risks.  Harv Rev Psychiatry 2007;15 (4) 133- 145

Isacsson  GHolmgren  AOsby  UAhlner  J Decrease in suicide among the individuals treated with antidepressants: a controlled study of antidepressants in suicide, Sweden 1995-2005.  Acta Psychiatr Scand 2009;120 (1) 37- 44

Haverkampf, C. J. (2010a). Communication and Therapy (3rd ed.). Dublin: Psychiatry Psychotherapy Communication Publishing Ltd.

Haverkampf, C. J. (2010b). Inner Communication (3rd ed.). Dublin: Psychiatry Psychotherapy Communication Publishing Ltd.

Haverkampf, C. J. (2012a). A Case of Psychosis. J Psychiatry Psychotherapy Communication, 1(3), 61–67.

Haverkampf, C. J. (2012b). Economic Costs of Depression. J Psychiatry Psychotherapy Communication, 1(2), 20–26.

Haverkampf, C. J. (2017a). Communication-Focused Therapy (CFT) (2nd ed.). Dublin: Psychiatry Psychotherapy Communication Publishing Ltd.

Haverkampf, C. J. (2017b). Depression and Medication (3). Retrieved from https://www.jonathanhaverkampf.com/

Haverkampf, C. J. (2018a). An Overview of Psychiatric Medication (3rd ed.). Dublin: Psychiatry Psychotherapy Communication Publishing Ltd.

Haverkampf, C. J. (2018b). Beginning to Communicate (3rd ed.). Dublin: Psychiatry Psychotherapy Communication Publishing Ltd.

Haverkampf, C. J. (2018c). Building Meaning – Communication and Creativity (3rd ed.). Dublin: Psychiatry Psychotherapy Communication Publishing Ltd.

Haverkampf, C. J. (2018d). Communication-Focused Therapy (CFT) – Specific Diagnoses (Vol II) (2nd ed.). Dublin: Psychiatry Psychotherapy Communication Publishing Ltd.

Kessler  RCBerglund  PBorges  GNock  MWang  PS Trends in suicide ideation, plans, gestures, and attempts in the United States, 1990-1992 to 2001-2003.  JAMA 2005;293 (20) 2487- 2495

US Food and Drug Administration Summary minutes of the CDER Psychopharmacologic Drugs Advisory Committee and the FDA Pediatric Advisory Committee, September 13-14, 2004. http://www.fda.gov/ohrms/dockets/ac/04/minutes/2004-4065M1_Final.htm.

Hammad  TALaughren  TRacoosin  J Suicidality in pediatric patients treated with antidepressant drugs.  Arch Gen Psychiatry 2006;63 (3) 332- 339PubMedGoogle ScholarCrossref

US Food and Drug Administration Overview for December 13 Meeting of Psychopharmacologic Drugs Advisory Committee (PDAC). http://www.fda.gov/ohrms/dockets/ac/06/briefing/2006-4272b1-01-FDA.pdf.

Gunnell  DSaperia  JAshby  D Selective serotonin reuptake inhibitors (SSRIs) and suicide in adults: meta-analysis of drug company data from placebo controlled, randomised controlled trials submitted to the MHRA’s safety review.  BMJ 2005;330 (7488) 385

Saperia  JAshby  DGunnell  D Suicidal behaviour and SSRIs: updated meta-analysis.  BMJ 2006;332 (7555) 1453

Hammad  TALaughren  TPRacoosin  JA Suicide rates in short-term randomized controlled trials of newer antidepressants.  J Clin Psychopharmacol 2006;26 (2) 203- 207

Jick  HKaye  JJick  S Antidepressants and the risk of suicidal behaviors.  JAMA 2004;292 (3) 338- 343

Martinez  CRietbrock  SWise  LAshby  DChick  JMoseley  JEvans  SGunnell  D Antidepressant treatment and the risk of fatal and non-fatal self-harm in first episode depression: nested case-control study.  BMJ 2005;330 (7488) 389

Simon  GESavarino  JOperskalski  BWang  PS Suicide risk during antidepressant treatment.  Am J Psychiatry 2006;163 (1) 41- 47

Valuck  RJLibby  AMSills  MRGiese  AAAllen  RR Antidepressant treatment and risk of suicide attempt by adolescents with major depressive disorder: a propensity-adjusted retrospective cohort study.  CNS Drugs 2004;18 (15) 1119- 1132

Rubino  ARoskell  NTennis  PMines  DWeich  SAndrews  E Risk of suicide during treatment with venlafaxine, citalopram, fluoxetine, and dothiepin: retrospective cohort study.  BMJ 2007;334 (7587) 242

Juurlink  DNMamdani  MMKopp  ARedelmeier  DA The risk of suicide with selective serotonin reuptake inhibitors in the elderly.  Am J Psychiatry 2006;163 (5) 813- 821

Fazel  SGrann  MAhlner  JGoodwin  G Suicides by violent means in individuals taking SSRIs and other antidepressants: a postmortem study in Sweden, 1992-2004.  J Clin Psychopharmacol 2007;27 (5) 503- 506

British Columbia Ministry of Health Services PharmaNet. http://www.health.gov.bc.ca/pharmacare/pharmanet/netindex.html.

Williams  JIYoung  W Inventory of Studies on the Accuracy of Canadian Health Administrative Databases.  Toronto, ON: Institute for Clinical Evaluative Sciences; 1996

Pharmaceutical Services Division, Ministry of Health Services, Government of British Columbia BC PharmaCare Annual Performance Report 2005. http://www.health.gov.bc.ca/pharmacare/pdf/APROnline.pdf.

Dormuth  CRGlynn  RJNeumann  PMaclure  MBrookhart  AMSchneeweiss  S Impact of two sequential drug cost-sharing policies on the use of inhaled medications in older patients with chronic obstructive pulmonary disease or asthma.  Clin Ther2006286964978, discussion 962-963

Dormuth  CRSchneeweiss  SBrookhart  MACarney  GBassett  KAdams  SWright  JM Frequency and predictors of tablet splitting in statin prescriptions: a population-based analysis.  Open Med 2008;2 (3) e5- e13

Kwon  ABungay  KMPei  YRogers  WHWilson  IBZhou  QAdler  DA Antidepressant use: concordance between self-report and claims records.  Med Care 2003;41 (3) 368- 374

Johnson  REVollmer  WM Comparing sources of drug data about the elderly.  J Am Geriatr Soc 1991;39 (11) 1079- 1084

World Health Organization International Classification of Diseases, Ninth Revision (ICD-9).  Geneva, Switzerland: World Health Organization; 1977

World Health Organization International Statistical Classification of Diseases, 10th Revision (ICD-10).  Geneva, Switzerland: World Health Organization; 1992

Canadian Institute for Health Information Abstracting Manual.  Ottawa, ON: Canadian Institute for Health Information; 1999

Clark  DEDeLorenzo  MALucas  FLWennberg  DE Epidemiology and short-term outcomes of injured Medicare patients.  J Am Geriatr Soc 2004;52 (12) 2023-2030

Iribarren  CSidney  SJacobs  DR  JrWeisner  C Hospitalization for suicide attempt and completed suicide: epidemiological features in a managed care population.  Soc Psychiatry Psychiatr Epidemiol 2000;35 (7) 288-296

LeMier  MCummings  PWest  TA Accuracy of external cause of injury codes reported in Washington State hospital discharge records.  Inj Prev 2001;7 (4) 334-338

Moyer  LABoyle  CAPollock  DA Validity of death certificates for injury-related causes of death.  Am J Epidemiol 1989;130 (5) 1024-1032

Warburton  RN Takeup of income-tested health-care premium subsidies: evidence and remedies for British Columbia.  Can Tax J 2005;53 (1) 1-28

Charlson  MEPompei  PAles  KLMacKenzie  CR A new method of classifying prognostic comorbidity in longitudinal studies: development and validation.  J Chronic Dis 1987;40 (5) 373-383

Cipriani  AFurukawa  TASalanti  GGeddes  JRHiggins  JPChurchill  RWatanabe  NNakagawa  AOmori  IMMcGuire  HTansella  MBarbui  C Comparative efficacy and acceptability of 12 new-generation antidepressants: a multiple-treatments meta-analysis.  Lancet 2009;373 (9665) 746-758

Braitman  LERosenbaum  PR Rare outcomes, common treatments: analytic strategies using propensity scores.  Ann Intern Med 2002;137 (8) 693- 695

Schneeweiss  SPatrick  ARStürmer  TBrookhart  MAAvorn  JMaclure  MRothman  KJGlynn  RJ Increasing levels of restriction in pharmacoepidemiologic database studies of elderly and comparison with randomized trial results.  Med Care 2007;45 (10 (suppl 2)) S131-S142

Schneeweiss  SRassen  JAGlynn  RJAvorn  JMogun  HBrookhart  MA High-dimensional propensity score adjustment in studies of treatment effects using health care claims data.  Epidemiology 2009;20 (4) 512-522

Maldonado  GGreenland  S Simulation study of confounder-selection strategies.  Am J Epidemiol 1993;138 (11) 923-936

Fergusson  DDoucette  SGlass  KCShapiro  SHealy  DHebert  PHutton  B Association between suicide attempts and selective serotonin reuptake inhibitors: systematic review of randomised controlled trials [published correction appears in BMJ. 2005;330(7492):653].  BMJ 2005;330 (7488) 396

British Columbia Coroners Service Suicide statistics, 1997-2004. http://www.pssg.gov.bc.ca/coroners/publications/docs/stats-suicide-1997-2004.pdf.

BCStats British Columbia population by selected age groups. http://www.bcstats.gov.bc.ca/data/pop/pop/project/bc0806tab3.csv.

Schneeweiss  SAvorn  J A review of uses of health care utilization databases for epidemiologic research on therapeutics.  J Clin Epidemiol 2005;58 (4) 323-337

Hawton  Kvan Heeringen  K Suicide.  Lancet 2009;373 (9672) 1372-1381

Greenland  SRobins  J Confounding and misclassification.  Am J Epidemiol 1985;122 (3) 495-506

Stahl  SMGrady  MMMoret  CBriley  M SNRIs: their pharmacology, clinical efficacy, and tolerability in comparison with other classes of antidepressants.  CNS Spectr 2005;10 (9) 732-747

Rush  AJTrivedi  MHWisniewski  SRStewart  JWNierenberg  AAThase  MERitz  LBiggs  MMWarden  DLuther  JFShores-Wilson  KNiederehe  GFava  MSTAR*D Study Team, Bupropion-SR, sertraline, or venlafaxine-XR after failure of SSRIs for depression.  N Engl J Med 2006;354 (12) 1231-1242

Mines  DHill  DYu  HNovelli  L Prevalence of risk factors for suicide in patients prescribed venlafaxine, fluoxetine, and citalopram.  Pharmacoepidemiol Drug Saf 2005;14 (6) 367-372

Kelsey  JLWhittemore  ASEvans  ASThompson  WD Methods in Observational Epidemiology. 2nd ed. New York, NY: Oxford University Press; 1996

Centers for Disease Control and Prevention Web-Based Injury Statistics Query and Reporting System (WISQARS), 2006. http://www.cdc.gov/ncipc/wisqars.

Middleton N, Gunnell D, Whitley E, Dorling D, Frankel S. Secular trends in antidepressant prescribing in the UK, 1975-1998. J Public Health Med 2001;23: 262-7.

Isacsson G. Suicide prevention—a medical breakthrough? Acta Psychiatr Scand 2000;102: 113-7.

Barbui C, Campomori A, D’Avanzo B, Negri E, Garattini S. Antidepressant drug use in Italy since the introduction of SSRIs: national trends, regional differences and impact on suicide rates. Soc Psychiatry Psychiatr Epidemiol 1999;34: 152-6.

Hall WD, Mant A, Mitchell PB, Rendle VA, Hickie IB, McManus P. Association between antidepressant prescribing and suicide in Australia, 1991-2000: trend analysis. BMJ 2003;326: 1008.

Rihmer Z, Belso N, Kalmar S. Antidepressants and suicide prevention in Hungary. Acta Psychiatr Scand 2001;103: 238-9.

Olfson M, Shaffer D, Marcus SC, Greenberg T. Relationship between antidepressant medication treatment and suicide in adolescents. Arch Gen Psychiatry 2003;60: 978-82.

Healy D. Lines of evidence on the risks of suicide with selective serotonin reuptake inhibitors. Psychother Psychosom 2003;72: 71-9.

Medawar C, Herxheimer A, Bell A, Jofre S. Paroxetine, Panorama and user reporting of ADRs: Consumer intelligence matters in clinical practice and post-marketing drug surveillance. Int J Risk Saf Med 2002;15: 161-9.

SSRI and venlafaxine use in children. Curr Prob Pharmacovig 2003;29: 4.

Freemantle N, Long A, Mason J, Sheldon T, Song F, Watson P, et al. Effective health care: the treatment of depression in primary care. Leeds: University of Leeds; Department of Health, 1993.

MacGillivray S, Arroll B, Hatcher S, Ogston S, Reid I, Sullivan F et al. Efficacy and tolerability of selective serotonin reuptake inhibitors compared with tricyclic antidepressants in depression treated in primary care: systematic review and meta-analysis. BMJ 2003;326: 1014-9.

Whittington CJ, Kendall T, Fonagy P, Cottrell D, Cotgrove A, Boddington E. Selective serotonin reuptake inhibitors in childhood depression: systematic review of published versus unpublished data. Lancet 2004;363: 1341-5.

Rutz W, von Knorring L, Walinder J. Long-term effects of an educational program for general practitioners given by the Swedish committee for the prevention and treatment of depression. Acta Psychiatr Scand 1992;85: 83-8.

Beasley CM Jr, Dornseif BE, Bosomworth JC, Sayler ME, Rampey AH, Heiligenstein JH. Fluoxetine and suicide: a meta-analysis of controlled trials of treatment for depression. BMJ 1991;303: 685-92.

Khan A, Khan S, Kolts R, Brown WA. Suicide rates in clinical trials of SSRIs, other antidepressants, and placebo: analysis of FDA reports. Am J Psychiatry 2003;160: 790-2.

Jick SS, Dean AD, Jick H. Antidepressants and suicide. BMJ 1995;310: 215-8.

Oravecz R, Czigler B, Leskosek F. Correlation between suicide rate and antidepressant use in Slovenia. Arch Suicide Res 2003;7: 279-85.

Helgason T, Tomasson H, Zoega T. Antidepressants and public health in Iceland. Time series analysis of national data. Br J Psychiatry 2004;184: 157-62.

Gunnell D, Middleton N, Whitley E, Dorling D, Frankel S. Why are suicide rates rising in young men but falling in the elderly?—a time-series analysis of trends in England and Wales 1950-1998. Soc Sci Med 2003;57: 595-611.

Amos T, Appleby L, Kiernan K. Changes in rates of suicide by car exhaust asphyxiation in England and Wales. Psychol Med 2001;31: 935-9.

Shah R, Uren Z, Baker A, Majeed A. Deaths from antidepressants in England and Wales 1993-1997: analysis of a new national database. Psychol Med 2001;31: 1203-10.

Freemantle N, House A, Song F, Mason JM, Sheldon TA. Prescribing selective serotonin reuptake inhibitors as strategy for prevention of suicide. BMJ 1994;309: 249-53.

Teicher MH, Glod C, Cole JO. Emergence of intense suicidal preoccupation during fluoxetine treatment. Am J Psychiatry 1990;147: 207-10.

Masand P, Gupta S, Dewan M. Suicidal ideation related to fluoxetine treatment. N Engl J Med 1991;324: 420.

Als-Nielsen B, Chen W, Gluud C, Kjaergard LL. Association of funding and conclusions in randomized drug trials. JAMA 2003;290: 921-6.

Medicines and Healthcare Products Regulatory Agency. Selective serotonin reuptake inhibitors (SSRIs): overview of regulatory status and CSM advice relating to major depressive disorder (MDD) in children and adolescents including a summary of available safety and efficacy data. http://medicines.mhra.gov.uk/ourwork/monitorsafequalmed/safetymessages/ssrioverview_101203.htm

Nutt D. Death and dependence: current controversies over the selective serotonin reuptake inhibitors. J Psychopharmacol 2003;17: 355-64.

MacKay FR, Dunn NR, Martin RM, Pearce GL, Freemantle SN, Mann RD. Newer antidepressants: a comparison of tolerability in general practice. Br J Gen Pract 1999;49: 892-6.

McClure GMG. Suicide in children and adolescents in England and Wales 1970-1998. Br J Psychiatry 2001;178: 469-74.

Hawton K, Hall S, Simkin S, Bale L, Bond A, Codd S, et al. Deliberate selfharm in adolescents: a study of characteristics and trends in Oxford, 1990-2000. J Child Psychol Psychiatry 2003;44: 1191-8.

Donoghue JM, Tylee A. The treatment of depression: prescribing patterns of antidepressants in primary care in the UK. Br J Psychiatry 1996;168: 164-8. [PubMed]

Paykel ES, Priest RG. Recognition and management of depression in general practice: consensus statement. BMJ 1992;305: 1198-202. [PMC free article] [PubMed]

Harris EC, Barraclough B. Excess mortality of mental disorder. Br J Psychiatry 1998;173: 11-53.

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