Depression The Dos, the Don ts, the Despair An Update on Treatment

1. DepressionThe Dos, the Don’ts, the DespairAn Update on Treatment Moderator Summary None Found User Notes None FoundModerator Summary None Found User Notes None Found

2. Presented by (at different venues)Dr Andrew DarbyDr Adrian LeathartDr Mani MaharajhDr Colin Patrick Moderator Summary None Found User Notes None FoundModerator Summary None Found User Notes None Found

3. Goals of presentation Provide a forum for discussion Significant rate of depression and comorbid illness Impact of depression Areas of specific interest Pregnancy Adolescents Associated anxiety Treatment options Responders Treatment resistance Effectiveness of treatments

4. Depression Moderator Summary Studies carried out in general health services have demonstrated that, on average, 10% of all contacts with general healthcare services occur because of the presence of a depressive disorder. These findings have been duplicated a number of times and in different parts of the world. A discrepancy exists between the prevalence of depression and the percentage of cases which are recognised. The World Health Organisation figures show the actual average length of treatment for depression is 3 to 4 months, compared with their recommendation of 12 months. User Notes None FoundModerator Summary Studies carried out in general health services have demonstrated that, on average, 10% of all contacts with general healthcare services occur because of the presence of a depressive disorder. These findings have been duplicated a number of times and in different parts of the world. A discrepancy exists between the prevalence of depression and the percentage of cases which are recognised. The World Health Organisation figures show the actual average length of treatment for depression is 3 to 4 months, compared with their recommendation of 12 months. User Notes None Found

5. Possible consequences of depression Moderator Summary None Found User Notes None FoundModerator Summary None Found User Notes None Found

6. Impact of depression Depression is usually a chronic, disabling & relapsing condition – 80% relapse within 5 years. It is sometimes difficult to separate causes and consequences of depression. Among the consequences of depression are domains of social, physical and psychological disabilities. Moderator Summary The consequences of depression are far reaching and their impact extends to social, marital, familial, physical, cognitive and psychological domains. The most dreaded consequence of depression is suicide. User Notes None FoundModerator Summary The consequences of depression are far reaching and their impact extends to social, marital, familial, physical, cognitive and psychological domains. The most dreaded consequence of depression is suicide. User Notes None Found

7. Impact of depression Pregnancy and postnatally suicidal behaviour poor self-care inadequate nutrition excessive use of alcohol and cigarettes poor antenatal clinic attendance increased rates of prematurity low birth weight irritability in newborns Increased depression risk in adolescence and adulthood Moderator Summary Significantly more people with major depression (compared to non-sufferers) report impairment in the great majority of functional domains evaluated. These data are in line with annual cost estimates for mood disorders, in which absenteeism and reduced productivity are the two largest cost categories. User Notes None FoundModerator Summary Significantly more people with major depression (compared to non-sufferers) report impairment in the great majority of functional domains evaluated. These data are in line with annual cost estimates for mood disorders, in which absenteeism and reduced productivity are the two largest cost categories. User Notes None Found

8. The leading causes of disability for both sexes in developed countries Moderator Summary Disability is defined as years lived with disability. User Notes None FoundModerator Summary Disability is defined as years lived with disability. User Notes None Found

9. Suicide rate per country Moderator Summary See mortality rates. User Notes None FoundModerator Summary See mortality rates. User Notes None Found

10. Depression in the 20th century Moderator Summary None Found User Notes None FoundModerator Summary None Found User Notes None Found

11. Depression in the 20th century Moderator Summary In the 1980s, several studies investigated either lifetime rate of depression by birth cohort in epidemiology surveys or frequency of depression in relatives of patients with affective disorders. The conclusions of these studies were that frequency of depressive episodes increased and age at first episode decreased in younger cohorts throughout this century. User Notes None FoundModerator Summary In the 1980s, several studies investigated either lifetime rate of depression by birth cohort in epidemiology surveys or frequency of depression in relatives of patients with affective disorders. The conclusions of these studies were that frequency of depressive episodes increased and age at first episode decreased in younger cohorts throughout this century. User Notes None Found

12. General population and mood disorders Approximately 60-70% of adults in the general population will at some time during their lives suffer from depression or anxiety sufficient to affect their daily activities. Moderator Summary Learning objectives Participants should know the frequency of depression in primary care, the proportion of cases that are missed, the presentation of cases in primary care. (Supporting slide for vote.) User Notes None FoundModerator Summary Learning objectives Participants should know the frequency of depression in primary care, the proportion of cases that are missed, the presentation of cases in primary care. (Supporting slide for vote.) User Notes None Found

13. Age at onset of depression Moderator Summary This prospective study confirms other data gathered in the 1980s, showing that nowadays depression is more common among younger adults. User Notes None FoundModerator Summary This prospective study confirms other data gathered in the 1980s, showing that nowadays depression is more common among younger adults. User Notes None Found

14. Diagnosis and classification Moderator Summary The Recognition workshop examines: Diagnosis and classification. Historical aspects. Concepts of depression and diagnosis of depressive disorders. Classifications of mood disorders (DSM-ICD). Diagnostic criteria (DSM-ICD). Differential diagnosis (normal grief, other mental disorders). This section describes the present concepts for the diagnosis of depression and the most widely used classification systems for mood disorders (DSM–ICD). This description will include unipolar major depression and all other mood disorders important for the differential diagnosis of depression. User Notes None FoundModerator Summary The Recognition workshop examines: Diagnosis and classification. Historical aspects. Concepts of depression and diagnosis of depressive disorders. Classifications of mood disorders (DSM-ICD). Diagnostic criteria (DSM-ICD). Differential diagnosis (normal grief, other mental disorders). This section describes the present concepts for the diagnosis of depression and the most widely used classification systems for mood disorders (DSM–ICD). This description will include unipolar major depression and all other mood disorders important for the differential diagnosis of depression. User Notes None Found

15. General practice patients and recognised major depression How do patients with major depression usually present in primary care? Moderator Summary Learning objectives Participants should know the frequency of depression in primary care, the proportion of cases that are missed, the presentation of cases in primary care. (Supporting slide for vote.) User Notes None FoundModerator Summary Learning objectives Participants should know the frequency of depression in primary care, the proportion of cases that are missed, the presentation of cases in primary care. (Supporting slide for vote.) User Notes None Found

16. Key symptoms Emotional Physical Moderator Summary None Found User Notes None FoundModerator Summary None Found User Notes None Found

17. Other key symptoms Mood disturbances may include: irritability and anxiety in addition or instead of pure depression symptoms predominant somatic symptoms headache general aches and pains libido decrease High male tendency to suicide seems due to unrecognised and untreated depression. Males don’t describe depression but: Tiredness Loss of energy Malaise Possible anger Moderator Summary None Found User Notes None FoundModerator Summary None Found User Notes None Found

18. Case study 1 She complained that every time she listened to music on the radio she thought it pulled the muscles of her head over to the left side. She was convinced there was "nothing inside her back" and that her motions were "coming through her front passage". Her appetite had been poor, and she had lost 10kg in weight. She also slept badly and although she woke at 5 o'clock in the morning, it took her a long time to get going. She was frightened of being alone, so her 78-year-old sister was unable to leave her. Moderator Summary Learning objectives Participants should know the frequency of depression in primary care, the proportion of cases that are missed, the presentation of cases in primary care. User Notes None FoundModerator Summary Learning objectives Participants should know the frequency of depression in primary care, the proportion of cases that are missed, the presentation of cases in primary care. User Notes None Found

19. Questions for group discussion (2-3 people / group) Moderator Summary Learning objectives Participants should know the frequency of depression in primary care, the proportion of cases that are missed, the presentation of cases in primary care. User Notes None FoundModerator Summary Learning objectives Participants should know the frequency of depression in primary care, the proportion of cases that are missed, the presentation of cases in primary care. User Notes None Found

20. Case Study 1 What will be your first treatment? Moderator Summary These are the responses from the participants’ pre-meeting questionnaire. User Notes None FoundModerator Summary These are the responses from the participants’ pre-meeting questionnaire. User Notes None Found

21. Case Study 1 If you chose pharmacological treatment, which class of drug would you use? Moderator Summary These are the responses from the participants’ pre-meeting questionnaire. User Notes None FoundModerator Summary These are the responses from the participants’ pre-meeting questionnaire. User Notes None Found

22. Case Study 1 If you chose psychological treatment, which type of therapy would you use? Moderator Summary These are the responses from the participants’ pre-meeting questionnaire. User Notes None FoundModerator Summary These are the responses from the participants’ pre-meeting questionnaire. User Notes None Found

23. Children and adolescents Moderator Summary None Found User Notes None FoundModerator Summary None Found User Notes None Found

24. Child and adolescent depression - an overview Depression in children and adolescents is more common now than in previous generations. In pre-pubertal children prevalence of depression is in the range of 0.5-2.0%. After puberty, prevalence increases immensely and there appears to be a marked female preponderance especially after 15 yrs of age. Juvenile depression is recurrent with a high risk of suicide. Moderator Summary Depression in children and adolescents is rapidly becoming a major healthcare issue. Rates in children are much lower than in adolescents. However, occurrence and suicide make this an especially fragile population. User Notes None FoundModerator Summary Depression in children and adolescents is rapidly becoming a major healthcare issue. Rates in children are much lower than in adolescents. However, occurrence and suicide make this an especially fragile population. User Notes None Found

25. Differential diagnosis in children: general guidelines Moderator Summary Early-onset depression and dysthymic disorder are frequent, recurrent and familial disorders. Major depression occurs at an earlier age in successive cohorts and is now an important issue in the differential diagnosis of many childhood psychiatric and medical conditions. User Notes None FoundModerator Summary Early-onset depression and dysthymic disorder are frequent, recurrent and familial disorders. Major depression occurs at an earlier age in successive cohorts and is now an important issue in the differential diagnosis of many childhood psychiatric and medical conditions. User Notes None Found

26. Systemic and central nervous system disorders mimicking depression in children Moderator Summary Disorders of almost any organ system are to be considered in the differential diagnosis of depression in children. The crucial point is to recognise course, age of onset and common features in relation to the child’s status. User Notes None FoundModerator Summary Disorders of almost any organ system are to be considered in the differential diagnosis of depression in children. The crucial point is to recognise course, age of onset and common features in relation to the child’s status. User Notes None Found

27. Case study 2 - Frank Frank's problems are as follows: dropped out of school, no job, lack of interest, unhappy, not sleeping, lack of energy, alcohol (and sometimes drug) abuse. Moderator Summary This is the background to the case story about Frank. This graphic should be viewed with the several questionnaire responses associated with this case. User Notes None FoundModerator Summary This is the background to the case story about Frank. This graphic should be viewed with the several questionnaire responses associated with this case. User Notes None Found

28. Questions for group discussion (2-3 people / group) Moderator Summary Learning objectives Participants should know the frequency of depression in primary care, the proportion of cases that are missed, the presentation of cases in primary care. User Notes None FoundModerator Summary Learning objectives Participants should know the frequency of depression in primary care, the proportion of cases that are missed, the presentation of cases in primary care. User Notes None Found

29. Case study 2 What will be your first treatment? Moderator Summary These are the responses from the participants’ pre-meeting questionnaire. User Notes None FoundModerator Summary These are the responses from the participants’ pre-meeting questionnaire. User Notes None Found

30. Case Study 2 If you chose pharmacological treatment, which class of drugs would you use? Moderator Summary These are the responses from the participants’ pre-meeting questionnaire. User Notes None FoundModerator Summary These are the responses from the participants’ pre-meeting questionnaire. User Notes None Found

31. Case Study 2 If you chose psychological treatment, which type of therapy would you use? Moderator Summary These are the responses from the participants’ pre-meeting questionnaire. User Notes None FoundModerator Summary These are the responses from the participants’ pre-meeting questionnaire. User Notes None Found

32. Co-morbidity Moderator Summary None Found User Notes None FoundModerator Summary None Found User Notes None Found

33. Anxiety and depression Moderator Summary None Found User Notes None FoundModerator Summary None Found User Notes None Found

34. Anxiety disorders and depression Anxiety symptoms are common in depressive disorders. Depression is a common complication of anxiety states. Anxiety first presenting after the age of 40 years favours diagnosis of depression. Periodic mono-symptomatic phobic and obsessional states may be regarded as affective equivalents. Moderator Summary As the controversy between ‘splitters’ (anxiety versus depression) and ‘lumpers’ (continuous concept) in the diagnosis of anxiety and depression is yet unresolved, clinical variables that distinguish between these entities are needed. User Notes None FoundModerator Summary As the controversy between ‘splitters’ (anxiety versus depression) and ‘lumpers’ (continuous concept) in the diagnosis of anxiety and depression is yet unresolved, clinical variables that distinguish between these entities are needed. User Notes None Found

35. Moderator Summary The World Health Organisation (WHO) collaborative study on psychological problems in general healthcare investigated the form, frequency, course and outcome of common psychological problems in primary-care settings at 15 international sites. A total of 25,916 adults who consulted healthcare services were interviewed. Possible or borderline cases of mental disorder and a sample of known cases were followed-up at 3 months and 1 year. Using standard diagnostic algorithms (ICD-10), prevalence rates were calculated for current disorder (1-month data) and lifetime experience of the disorder. Well-defined psychological problems were frequent in all of the general healthcare settings examined (median 24.0%). Among the most common disorders were depression anxiety, alcohol misuse, somatoform disorders and neurasthenia. Approximately 9% of patients suffered from a ‘sub-threshold condition’ that did not meet diagnostic criteria, but had clinically significant symptoms and functional impairment. The most common co-occurrence was depression and anxiety. Co-morbidity increases the likelihood of recognition of mental disorders in general healthcare and the likelihood of receiving treatment. User Notes None FoundModerator Summary The World Health Organisation (WHO) collaborative study on psychological problems in general healthcare investigated the form, frequency, course and outcome of common psychological problems in primary-care settings at 15 international sites. A total of 25,916 adults who consulted healthcare services were interviewed. Possible or borderline cases of mental disorder and a sample of known cases were followed-up at 3 months and 1 year. Using standard diagnostic algorithms (ICD-10), prevalence rates were calculated for current disorder (1-month data) and lifetime experience of the disorder. Well-defined psychological problems were frequent in all of the general healthcare settings examined (median 24.0%). Among the most common disorders were depression anxiety, alcohol misuse, somatoform disorders and neurasthenia. Approximately 9% of patients suffered from a ‘sub-threshold condition’ that did not meet diagnostic criteria, but had clinically significant symptoms and functional impairment. The most common co-occurrence was depression and anxiety. Co-morbidity increases the likelihood of recognition of mental disorders in general healthcare and the likelihood of receiving treatment. User Notes None Found

36. Panic disorder Moderator Summary None Found User Notes None FoundModerator Summary None Found User Notes None Found

37. Lifetime co-morbidity of panic attacks and major depression Symptom profiles and rates of co-morbidity of panic attacks and major depression in over 12,600 patients were examined. Lifetime co-occurrence was 11 times higher than expected by chance (40%-50%). More severe depression with more suicide attempts was more frequent in the co-morbid group. Anxiety disorders: lifetime prevalence 14.6%Panic disorders: lifetime prevalence 1.6% Moderator Summary The co-occurrence of panic attacks and depression is common. Although symptom profiles are similar in depression alone or depression with co-morbid panic, greater severity is the rule when the two disorders occur in the same individual. User Notes None FoundModerator Summary The co-occurrence of panic attacks and depression is common. Although symptom profiles are similar in depression alone or depression with co-morbid panic, greater severity is the rule when the two disorders occur in the same individual. User Notes None Found

38. Management of Panic Attacks / Anxiety What would your treatment ideally include? Biological Psychological Combined Other If you chose pharmacological treatment, which class of drugs would you use? TCA SSRI MAOI SNRI Benzodiazepine Beta-Blocker Antihistamine Other Moderator Summary The co-occurrence of panic attacks and depression is common. Although symptom profiles are similar in depression alone or depression with co-morbid panic, greater severity is the rule when the two disorders occur in the same individual. User Notes None FoundModerator Summary The co-occurrence of panic attacks and depression is common. Although symptom profiles are similar in depression alone or depression with co-morbid panic, greater severity is the rule when the two disorders occur in the same individual. User Notes None Found

39. Benzodiazepines for depressed with anxiety Advantages Rapid and effective control of anxiety Help to decrease SSRI-initiation of therapy anxiety Decreases drop outs Increases short-term response up to four weeks. Disadvantages Increase in accident proneness (sedation and impaired cognition) Induce dependence (up to 1/3 of patients) Long half-life less habit forming that short half-life High potency more habit forming than low potency. Alprazolam > lorazepam > diazepam

40. Pregnancy and lactation Moderator Summary None Found User Notes None FoundModerator Summary None Found User Notes None Found

41. Depression during pregnancy Interviewing women during pregnancy to screen for depression is not often undertaken. Pregnancy is a period during which prevalence rates of depression are about double those of controls - reaching 24-29%. Many psychosocial factors are strongly related to the high rates of depression during pregnancy: poor social support low income detachment of partner family history of depression Moderator Summary Depression during pregnancy is not extensively studied. Several recent publications demonstrate that rates of depression double during this period. The occurrence of depression in pregnant women is strongly influenced by the following factors: social support, low income, anticipation of crowdedness in the home, lack or detachment of partner and family history or previous history of depression. User Notes None FoundModerator Summary Depression during pregnancy is not extensively studied. Several recent publications demonstrate that rates of depression double during this period. The occurrence of depression in pregnant women is strongly influenced by the following factors: social support, low income, anticipation of crowdedness in the home, lack or detachment of partner and family history or previous history of depression. User Notes None Found

42. Maternal depression during pregnancy and the postnatal period is associated with a significant disease burden Affects the mother Short- and long-term effects on the child. preterm delivery low birth weight operative delivery admission to neonatal intensive care units increased risk of adult depression.

43. Antidepressants in Pregnancy Number of studies examining several hundred infants with early exposure to SSRIs (Floxetine, Citalopram, Sertraline & Fluvoxamine) and older TCAs no increased risk of birth defects or malformations above the general population risk (2-3%, of which 1/3 are heart defects) Slight increase in prematurity (SSRI) 36/52 less evidence available on Venlafaxine – “ we suggest no increased risk of birth defects with first trimester exposure”. Very recent reports slight increase in the risk of heart defects (VSD) with SSRIs, in particular with Paroxetine. Reports remain conflicting. Currently Paroxetine is best avoided in pregnancy. Potential for neonatal withdrawal effects in late pregnancy

44. Clinical signs observed in newborns exposed to selective serotonin reuptake inhibitors in late pregnancy Most Common Irritability Restlessness Jitteriness Tremor Muscular hypotonia Rigidity Respiratory distress Feeding problems Less Common Incoordination Hyper-reflexia Myoclonus Increased muscle tonus Continuous crying Sleeping problems Convulsions

45. It is important to balance the mental health needs of the mother and the safety issues for the infant in the treatment of depression in pregnancy. The SSRIs (except possibly Paroxetine) do not appear to be associated with birth defects on the information currently available but further studies are in train to confirm this.

46. Recurrent Depression Moderator Summary None Found User Notes None FoundModerator Summary None Found User Notes None Found

47. Recurrence refers to the appearance of a new episode of major depression during the recovery period. Between 50-85% of patients who have a first episode will have at least one subsequent episode. The criterion for recurrent major depression is at least two episodes of major depression. Recurrent major depression Moderator Summary Once major depression becomes recurrent (that is, a second episode appears) the course of the ensuing illness changes significantly and the prognosis is poor. Recurrent unipolar major depression is characterised by extremely high relapse and recurrence rates and a significant increase in morbidity between episodes. Among such patients, 10–20% are likely to develop a chronic, unremitting clinical course and of those who recover, 50% will have another major depressive episode (recurrence) within the next two years. The risk of recurrence is greatest in the first 4–6 months after recovery and, although it remains high, levels off over the next 6–12 months. Significant residual symptoms will remain in up to 20–35 % of depressed patients. The pop-ups show the data from long-term, prospective, longitudinal studies of unipolar major depression in 173 patients, as reported in the last assessment carried out in 1980. The clinical course of these individuals is very chronic in nature, with over one-fifth (21%) of these patients’ lives spent suffering from a major depressive episode. The median number of episodes experienced by the unipolar depressive patients was four, with 25% of the sample experiencing six or more and some as many as 23. Only 30% of the patients achieved full remission from treatment and 13% experienced a chronic course. Finally, Angst reports evidence that the episode recurrence rate in these patients appeared to diminish significantly in those who were over 65 years of age. User Notes None FoundModerator Summary Once major depression becomes recurrent (that is, a second episode appears) the course of the ensuing illness changes significantly and the prognosis is poor. Recurrent unipolar major depression is characterised by extremely high relapse and recurrence rates and a significant increase in morbidity between episodes. Among such patients, 10–20% are likely to develop a chronic, unremitting clinical course and of those who recover, 50% will have another major depressive episode (recurrence) within the next two years. The risk of recurrence is greatest in the first 4–6 months after recovery and, although it remains high, levels off over the next 6–12 months. Significant residual symptoms will remain in up to 20–35 % of depressed patients. The pop-ups show the data from long-term, prospective, longitudinal studies of unipolar major depression in 173 patients, as reported in the last assessment carried out in 1980. The clinical course of these individuals is very chronic in nature, with over one-fifth (21%) of these patients’ lives spent suffering from a major depressive episode. The median number of episodes experienced by the unipolar depressive patients was four, with 25% of the sample experiencing six or more and some as many as 23. Only 30% of the patients achieved full remission from treatment and 13% experienced a chronic course. Finally, Angst reports evidence that the episode recurrence rate in these patients appeared to diminish significantly in those who were over 65 years of age. User Notes None Found

48. Course of depressive states Moderator Summary The relevant stages in the course of unipolar major depressive disorder. Presence of a depressive episode. Remission. Recovery. Relapse. Recurrence. All these definitions are derived from severity and time variables. User Notes None FoundModerator Summary The relevant stages in the course of unipolar major depressive disorder. Presence of a depressive episode. Remission. Recovery. Relapse. Recurrence. All these definitions are derived from severity and time variables. User Notes None Found

49. Maintenance treatment Moderator Summary Until recently, the need to continue antidepressant treatment after full recovery has been a controversial subject in the management of depression. However, this phase of treatment - defined as the maintenance treatment - is the best-studied means of reducing the risk of recurrent depression. These slides are intended to present the benefits of this important treatment phase. Data regarding the therapeutic options for maintenance treatment show efficacy, adequate length and dose of treatment and predictive factors. Long-term studies have consistently shown that major depressive disorder is classically a recurrent illness, with a recurrence rate as high as 50%. The question of the efficacy of long-term treatment (maintenance) is then crucial and may be investigated through long-term, placebo-controlled outcome studies. Differences may be observed according to the course of the illness; unipolar or bipolar. Pop-up C summarises some clinical variables which are important in determining which patient is likely to benefit from long-term maintenance antidepressant therapy. These factors are mainly derived from naturalistic observation studies. User Notes None FoundModerator Summary Until recently, the need to continue antidepressant treatment after full recovery has been a controversial subject in the management of depression. However, this phase of treatment - defined as the maintenance treatment - is the best-studied means of reducing the risk of recurrent depression. These slides are intended to present the benefits of this important treatment phase. Data regarding the therapeutic options for maintenance treatment show efficacy, adequate length and dose of treatment and predictive factors. Long-term studies have consistently shown that major depressive disorder is classically a recurrent illness, with a recurrence rate as high as 50%. The question of the efficacy of long-term treatment (maintenance) is then crucial and may be investigated through long-term, placebo-controlled outcome studies. Differences may be observed according to the course of the illness; unipolar or bipolar. Pop-up C summarises some clinical variables which are important in determining which patient is likely to benefit from long-term maintenance antidepressant therapy. These factors are mainly derived from naturalistic observation studies. User Notes None Found

50. Relapsing depression – a brainstorm How do we manage these patients? Suggestions from the floor

51. Predictors of long-term, maintenance antidepressant therapy Three episodes OR Moderator Summary Until recently, the need to continue antidepressant treatment after full recovery has been a controversial subject in the management of depression. However, this phase of treatment - defined as the maintenance treatment - is the best-studied means of reducing the risk of recurrent depression. These slides are intended to present the benefits of this important treatment phase. Data regarding the therapeutic options for maintenance treatment show efficacy, adequate length and dose of treatment and predictive factors. Long-term studies have consistently shown that major depressive disorder is classically a recurrent illness, with a recurrence rate as high as 50%. The question of the efficacy of long-term treatment (maintenance) is then crucial and may be investigated through long-term, placebo-controlled outcome studies. Differences may be observed according to the course of the illness; unipolar or bipolar. Pop-up C summarises some clinical variables which are important in determining which patient is likely to benefit from long-term maintenance antidepressant therapy. These factors are mainly derived from naturalistic observation studies. User Notes None FoundModerator Summary Until recently, the need to continue antidepressant treatment after full recovery has been a controversial subject in the management of depression. However, this phase of treatment - defined as the maintenance treatment - is the best-studied means of reducing the risk of recurrent depression. These slides are intended to present the benefits of this important treatment phase. Data regarding the therapeutic options for maintenance treatment show efficacy, adequate length and dose of treatment and predictive factors. Long-term studies have consistently shown that major depressive disorder is classically a recurrent illness, with a recurrence rate as high as 50%. The question of the efficacy of long-term treatment (maintenance) is then crucial and may be investigated through long-term, placebo-controlled outcome studies. Differences may be observed according to the course of the illness; unipolar or bipolar. Pop-up C summarises some clinical variables which are important in determining which patient is likely to benefit from long-term maintenance antidepressant therapy. These factors are mainly derived from naturalistic observation studies. User Notes None Found

52. Strategies for improving treatment outcomes Moderator Summary None Found User Notes None FoundModerator Summary None Found User Notes None Found

53. Acute treatment of a depressive episode Moderator Summary None Found User Notes None FoundModerator Summary None Found User Notes None Found

54. Continuation phase – IMPROVEMENT Moderator Summary None Found User Notes None FoundModerator Summary None Found User Notes None Found

55. Continuation phase – NO IMPROVEMENT Moderator Summary None Found Up to only 25% have had an adequate trial of medication, many of the other 75% had several different antidepressants but of inadequate dose or duration! User Notes None FoundModerator Summary None Found Up to only 25% have had an adequate trial of medication, many of the other 75% had several different antidepressants but of inadequate dose or duration! User Notes None Found

56. Practical issues with Antidepressants Moderator Summary None Found User Notes None FoundModerator Summary None Found User Notes None Found

57. General considerations about SSRIs Moderator Summary An important breakthrough in the development of antidepressants that combine selectivity for one neurotransmitter with minimal or no effect on adrenergic, histaminergic and cholinergic receptors came with the synthesis of the SSRIs. User Notes None FoundModerator Summary An important breakthrough in the development of antidepressants that combine selectivity for one neurotransmitter with minimal or no effect on adrenergic, histaminergic and cholinergic receptors came with the synthesis of the SSRIs. User Notes None Found

58. Comparative pharmacokinetic profiles of SSRIs Moderator Summary Kinetic profiles vary considerably among the SSRIs There are significant differences in drug handling between adults and elderly for citalopram, fluoxetine/norfluoxetine and paroxetine Little is currently known about the kinetic profiles in children and adolescents, although there is an increasing emphasis on research in these patient populations User Notes None FoundModerator Summary Kinetic profiles vary considerably among the SSRIs There are significant differences in drug handling between adults and elderly for citalopram, fluoxetine/norfluoxetine and paroxetine Little is currently known about the kinetic profiles in children and adolescents, although there is an increasing emphasis on research in these patient populations User Notes None Found

59. Inhibitory effects of SSRIs on drug metabolising CYP450 isoenzymes Moderator Summary Drug metabolism is usually a multi-step process that involves oxidation and conjugation of the oxidised metabolite. In the liver, the CYP450 system is broadly involved in the oxidation of many endogenous substances and detoxification of consumed substances (drugs, toxins, mutagens). Drugs such as the SSRIs can increase or decrease the functional activity of CYP enzymes. Drug-induced inhibition is usually competitive and occurs immediately, but the magnitude of the inhibition is a function of inhibitor concentration. The half-life of the inhibitor will determine the time taken to exert its full effect and, conversely, how long the inhibition will last after discontinuation. User Notes None FoundModerator Summary Drug metabolism is usually a multi-step process that involves oxidation and conjugation of the oxidised metabolite. In the liver, the CYP450 system is broadly involved in the oxidation of many endogenous substances and detoxification of consumed substances (drugs, toxins, mutagens). Drugs such as the SSRIs can increase or decrease the functional activity of CYP enzymes. Drug-induced inhibition is usually competitive and occurs immediately, but the magnitude of the inhibition is a function of inhibitor concentration. The half-life of the inhibitor will determine the time taken to exert its full effect and, conversely, how long the inhibition will last after discontinuation. User Notes None Found

60. Point prevalence per day of nausea Moderator Summary Nausea has most often been reported as the most troublesome adverse event at the onset of treatment with SSRIs. Often this is described as a transient effect. In this study the transient effect of this adverse event is demonstrated. The nausea peaks at day 4 and then there is a steady reduction in the reported rates. By day 21 the reported rates of nausea approach those of patients on placebo. User Notes None FoundModerator Summary Nausea has most often been reported as the most troublesome adverse event at the onset of treatment with SSRIs. Often this is described as a transient effect. In this study the transient effect of this adverse event is demonstrated. The nausea peaks at day 4 and then there is a steady reduction in the reported rates. By day 21 the reported rates of nausea approach those of patients on placebo. User Notes None Found

61. SSRI discontinuation reactions Usually mild, occasionally severe Begin 1-10 days after discontinuation (up to 24 days for fluoxetine) (Coupland et al, 1996) Highest incidence with paroxetine Symptoms include (Shatzberg et al, 1997): dysequilibrium (dizziness, vertigo, ataxia) gastrointestinal (nausea, vomiting) flu-like (fatigue, lethargy, myalgia, chills) sensory disturbance (parasthenia, electric shock sensations) sleep disturbance (vivid dreams, insomnia) psychic symptoms (agitation, anxiety, irritability) Moderator Summary The clinical relevance of antidepressant discontinuation reactions has received little attention. There have been few prospective randomised trials to determine the relative risk of discontinuation reactions with different SSRIs. Data from case reports, case series, clinical studies (post hoc analyses), retrospective incidence studies and post-marketing surveillance indicate that symptoms are more common with SSRIs with non-linear pharmacokinetics and relatively short half-lives (paroxetine and fluvoxamine; 10 and 11 hours, respectively, after single dose; Coupland et al., 1996; Lane, 1996). In addition, both these drugs inhibit their own metabolism. Discontinuation reactions appear to be associated with falls in SSRI plasma concentration at such a rate that the CNS does not have time to readjust to the decreasing concentration of drug. As both sertraline and citalopram have linear pharmacokinetics, their half-lives (26 and 33 hours, respectively) are not affected by plasma concentrations and rapid falls in drug levels do not occur. Although fluoxetine has non-linear pharmacokinetics, the half-lives of both parent drug and active metabolite nor-fluoxetine are very long, and falls in plasma concentration are therefore unlikely. The propensity for discontinuation reactions with paroxetine is only partly explained by the pharmacokinetics. Anticholinergicity of paroxetine may offer a further explanation (Owens et al., 1997). This may be compared with tricyclic antidepressants where discontinuation reactions have been attributed to cholinergic rebound. When ‘switching’ from one antidepressant to another, discontinuation reactions may be mistaken for poor toleration of the newly initiated antidepressant. Risk is usually reduced by tapering the dose, although this may be less effective with paroxetine. To avoid a long wash-out period after fluoxetine and reduce the risk of discontinuation reactions, use SSRIs with intermediate half-lives (citalopram, sertraline). User Notes None FoundModerator Summary The clinical relevance of antidepressant discontinuation reactions has received little attention. There have been few prospective randomised trials to determine the relative risk of discontinuation reactions with different SSRIs. Data from case reports, case series, clinical studies (post hoc analyses), retrospective incidence studies and post-marketing surveillance indicate that symptoms are more common with SSRIs with non-linear pharmacokinetics and relatively short half-lives (paroxetine and fluvoxamine; 10 and 11 hours, respectively, after single dose; Coupland et al., 1996; Lane, 1996). In addition, both these drugs inhibit their own metabolism. Discontinuation reactions appear to be associated with falls in SSRI plasma concentration at such a rate that the CNS does not have time to readjust to the decreasing concentration of drug. As both sertraline and citalopram have linear pharmacokinetics, their half-lives (26 and 33 hours, respectively) are not affected by plasma concentrations and rapid falls in drug levels do not occur. Although fluoxetine has non-linear pharmacokinetics, the half-lives of both parent drug and active metabolite nor-fluoxetine are very long, and falls in plasma concentration are therefore unlikely. The propensity for discontinuation reactions with paroxetine is only partly explained by the pharmacokinetics. Anticholinergicity of paroxetine may offer a further explanation (Owens et al., 1997). This may be compared with tricyclic antidepressants where discontinuation reactions have been attributed to cholinergic rebound. When ‘switching’ from one antidepressant to another, discontinuation reactions may be mistaken for poor toleration of the newly initiated antidepressant. Risk is usually reduced by tapering the dose, although this may be less effective with paroxetine. To avoid a long wash-out period after fluoxetine and reduce the risk of discontinuation reactions, use SSRIs with intermediate half-lives (citalopram, sertraline). User Notes None Found

62. Remission rates for TCA, SSRI and placebo in MELANCHOLIC depression (Perry, 1996) Moderator Summary The presence of melancholic features is associated with a minor placebo response rate. There is possibly a greater necessity for psychopharmacological treatments in melancholic depression. The presence of melancholic features is not a predictor of better response to active medication. Patients with moderate melancholic depression responded to a greater extent than those with severe melancholic depression (DSM) (Peselow, 1992). User Notes None FoundModerator Summary The presence of melancholic features is associated with a minor placebo response rate. There is possibly a greater necessity for psychopharmacological treatments in melancholic depression. The presence of melancholic features is not a predictor of better response to active medication. Patients with moderate melancholic depression responded to a greater extent than those with severe melancholic depression (DSM) (Peselow, 1992). User Notes None Found

63. Standard doses of antidepressants in major depression Moderator Summary None Found User Notes None FoundModerator Summary None Found User Notes None Found

64. Side-effect profiles of tricyclics and tetracyclics Moderator Summary None Found User Notes None FoundModerator Summary None Found User Notes None Found

66. Non-Pharmacological Interventions Moderator Summary None Found User Notes None FoundModerator Summary None Found User Notes None Found

67. Non-pharmacological Interventions Cognitive Behavioural Therapy Inter-Personal Therapy ‘Generic’ counselling not effective

68. What’s Next? GP Workshop in the planning for Depression and Anxiety Specific program Dynamic and interactive evidence based program Related to every day general practice CME accredited Day / weekend WATCH THIS SPACE