The lecture has been given on Nov. 23rd & 30th, 2010 by Dr. Nazar M. Mohammad Amin.

1. Mood Disorders 1

2. Mood Disorders History Depression was described in most of the Holy Books. It was thought to be due to evil spirits or as a punishment for angering the gods. Hippocrates (460–377 bc) described melancholia whom he thought as a brain disorder caused by excess of black bile. The concept of melancholia remained for many centuries with different explanations ranging from supernatural powers to changes in the blood. 2

3. Mood Disorders History Email kreaplin differentiated manic depressive illness from dementia praecox. His approach was mostly Biological while Sigmund Freud and Adolph Meyer in the middle of the 20th Century adopted a psychological approach to depression as introjection of anger towards loved objects. Deperssion was later classified into endogenous and neurotic depression, with the endogenous type thought to be responding to ECT. 3

4. Mood Disorders History Hippocrates described Mania too. Physicians throughout the centuries associated Melancholy with Mania. The term Bipolar disorder entered DSM III for the first time in 1980. British literature use the term affective disorders. Psychiatry Volume 8, Issue 4, Pages 107-144 (April 2009) 4

5. Mood Disorders Epidimiology The prevalence of mood disorders depend on the definition applied. An American study ( National Comorbidity Survey) found a life prevalence of 20.8% and an age of onset of 30 years. Lifetime prevalence of major depression is 4-19% of the population. It is twice in females as in males. Major age of onset is 25-30 years. 5

6. Mood Disorders Epidimiology Bipolar I disorder life time prevalence is 1-5%, for dysthymia is 3-7% and 0.5% for cyclothymia. The prevalence depends on the classification used . Major depressive disorder. Dysthymia Bipolar disorders. cyclothymia. Recurrent brief depressive disorder. Recurrent brief hypomania. Schizoaffective disorder. 6

7. Mood Disorders Epidimiology Onset is usually insidious for depression and more acute in mania. Mood disorders in general are recurrent and bipolar disorders usually have more episodes than unipolar disorders. Long term prognosis of mood disorders in general is better than that of schizophrenia and schizoafffective disorder. 7

8. Mood Disorders Epidimiology Patients with mood disorders have higher risk of suicide (15-30)% compared with the general population. Mortality from mood disorders especially depression is greater than in the general population. 8

9. Mood Disorders psychological models Cognitive behavioural models: Is based on five areas: social, cognitive, behaviour, physiololgical and mood. This model is based on the clinical features that maintain the patient’s current state and interfere with his improvement. Social include interpersonal, family, and marital problems. Cognitive include negative automatic thoughts and images, assumptions and schemas. 9

10. Mood Disorders psychological models Social model for depressive disorder In childhood sexual and physical abuse, parental indifference, loss of a parent. In adults social isolation, physical illness, unemployment, women with fulltime work and having three preschool childern.(Brown and Harris 1980). Psychodynamic model for depression Low actual self representation, insecure adult attachment and primitive superego. 10

11. Cognitive symptoms in mood disorders Coginitive disorders are important symptoms in mood disorders and some of the symptoms may remain even after remission. Impairments in memory, decision making are examples. Cognitive impairments indicate ventromedial prefrontal area involvement. The resilience of some pateints who do not develop mood disorders despite exposure to adverse environmental events is being studied to find ways of prevention of mood disorders. 11

12. Mood disorders clinical features Depression There are three groups of symptoms: emotional symptoms, psychomotor symptoms, and negative beliefs. Negative belief such as low self esteem and inappropriate guilt, feeling of hopelessness, helplessness and worthlessness. psychomotor symptomsinclude reduced movements, activity, facial expression, decreased verbal activity and withdrawal, increased activity such as agitation in the form of hand wringing to pacing. 12

13. Mood disorders clinical features Depression Affect is a relatively transient state of feeling depressed, sad or blue. Chronic depression is diagnosed when it lasts for more than two years. Double depression occurs when the patient has both major depression and dysthymia. 13

14. Mood disorders clinical features Mania The three cardinal symptoms of mania include: emotions, psychomotor symptoms, and expansiveness or increased self-esteem. The symptoms in hypomania are less sever than mania. There is elevated spirit mixed with irritability and hostility. There is decreased need for sleep and excessive motor activity. There is decreased concern about money with overspending and running into debts. There is inflated self esteem and overestimating one’s abilities. There is pressure of speech and loud speech. 14

15. Mood disorders clinical features Mania The patient might have psychotic symptoms as flights of ideas, excessive distractability and grandiose delusions. Unlike schizophrenia the psychotic symptoms are mood congruent. To diagnose hypomanic episode 4 days of symptoms are necessary and for a manic episode one week of symptoms is required. 15

16. Mood disordersDiagnosis and Classification There was a lot of confusion regarding classification of Mood Disorders. The DSM and ICD used different classifications. Nevertheless in the newer versions they got closer. Depression is both a mood or symptom and a syndrome. It is calssified into mild, moderate and sever. It could be a single episode or recurrent. 16

17. Mood disordersDiagnosis and Classification The symptoms must last for at least 14 days. They include loss of interest, lack of energy, impairment of sleep, appetite or concentration and suicidal thoughts. Dysthymia: a constant or recurrent mild depression lasting for at least two years. Manic states: in a manic episode the patient has elevated, expansive or irritable mood and other symptoms that could last for at least one week. 17

18. Mood disordersDiagnosis and Classification Bipolar I disorder is diagnosed when the patient has at least one manic episode. In the manic episode the patient Has elevated, expansive or irritable mood for at least one week. The condition is sever and requires hospitalization. Hypomania is less sever and does not require hospitalization and lasts for at least four days. Mania indicates bipolar I disorder and hypomania alternating with major depression indicates bipolar II disorder. 18

19. Mood disordersDiagnosis and Classification Both psychotic depression and melancholia were not adequately described in the classificaton systems available. Both ICD and DSM failed to specify the close association of depressive disorder and anxiety. Presence of anxiety could confuse the diagnosis. 19

20. Mood disordersDiagnosis and Classification Manic patients usually do not complaint of their symptoms and they are observed by realtives and their doctors. There is decreased need for sleep, disinhibition and increased energy. Robert Kendell Psychiatry 8:2 20

21. Mood disordersDiagnosis and Classification To diagnose any of the mood disorders the symptoms need to interfere with the life of the patient, must not be due to substance abuse, not secondary to another medical disorder and due to another mental disorder such as schizophrenia. 21

22. Brain structural changes inmood disorders Hippocampal volume is reduced in patients with major depressive disorder. Studies on both disorders bipolar disorder and major depressive disorder revealed changes in the amygdala too. Lithium and antidepressants produced changes in the gray matter size in some studies compared to preclinical data. Sophia frangou Psychiatry 8:4 22

23. Depression and diabetes mellitus Clinically significant depression is associated with a 65% increased risk of diabetes mellitus. Characteristics of depression frequently found in the community, namely nonsevere depression, persistent depression, and untreated depression, may play a role in the development of diabetes in a predominantly elderly adult population. Antonio Campayo, Peter de Jonge, Juan F Roy, Pedro Saz, Concepción de la Cámara, Miguel A. Quintanilla, Guillermo Marcos, Javier Santabárbara, and Antonio LoboAm J Psychiatry 2010 167: 580-588. 23

24. Depression in the elderly A study in Pakistan revealed an increase in the prevalence of depression in the elderly and they atributed that to the change in the family system from extended to nuclear system. Depression in the elderly: "Does family system play a role?" A cross-sectional study BMC Psychiatry 2007, 7:57 24

25. Management of mood disorders It is necessary that every patient, whom we suspect to have mood disorders, should be thoruoghly assessed by careful and full history and mental state examination. The notes of the social worker and clinical psychologists should be studied too. The necessary investigations to exclude other possible causes should be done including full blood count, drug screening , hormonal essays including thyroid function tests, EEG, CT scan and if necessary other neuroimaging techniques. 25

26. Management of mood disorders It is important to find out if the case in unipolar or part of a bipolar disorder. Risk assessment is a must to find out if the patient is a risk to himself in the form of suicide or self harm. The risk to others including homicidal risk is necessary too. The targets of our management should include the patient and the caregivers too. 26

27. Management of mood disorders The line of management depends on whether the disorder is acute or chronic, bipolar unipolar, recurrent or a single episode. The choice of the treatment method should be made by discussion with the patient, his relatives and individual physician. The treatment methods include: Psychological Pharmacological Physical 27

28. Management of mood disorders Psychological treatments According to the National Institute for Health and Clinical Excellence guideline for depression, psychological treatments are the treatments of choice for mild depressive episodes. In moderate depressive episodes they are an alternative to antidepressant medication, and for severe depressive episodes cognitive therapy in combination with antidepressants is the treatment of choice. Only cognitive therapy is established as effective in preventing the recurrence of depressive episodes. 28

29. Management of mood disorders Psychological treatments From an evidence-based perspective, cognitive therapy for depression is the best established psychological treatment for mood disorders. In contrast, psychological treatments can be effective in preventing recurrence of bipolar episodes, although there is little evidence for their effectiveness in acute bipolar episodes (depression, mania, hypomania, or mixed affective episodes). 29

30. Management of mood disorders Psychological treatments Psychological treatments for depression include: Cognitive therapy, behaviour therapy, cognitive behaviour therapy, problem solving, interpersonal therapy and psychodynamic therapy. Psychological treatment for bipolar disorder needs to be longer and includes psychoeducation, prevention of relapse and encouraging the patient to comply with the medication. Richard Morriss and Jan Scott Psychiatry 8:4 30

31. Pharmacologicalmanagement of unipolaraffective disorder In mild depression psychotherapy is the first line treatment and pharmacological therapy is not recommended routinely as first line therapy. In moderate to sever depression when other treatments for two weeks fail antidepressants should be first line treatment. In dysthymiaantidepressants could be used as first line treatment. R Hamish McAllister-Williams I Nicol Ferrier PSYCHIATR Y 8:4 113 © 2009 Elsevier Ltd. 31

32. Pharmacologicalmanagement of unipolaraffective disorder Tricyclic antidepressants: These drugs have many side effects including anticholinergic effects, hypotension and tachycardia and cardiac toxicity which makes them dangerous in toxicity and overdoses. Tricyclic antidepressants should not be used as first line treatment in mild to moderate depression. They are recommended for severely ill inpatients. 32

33. Pharmacologicalmanagement of unipolaraffective disorder Specific serotonin reuptake inhibitors: Including fluoxetene, paroxetene, fluvoxamine, citalopram, sertraline, escitalopram. They are recommended by NICE as first line pharmacological treatment of depression because they have less side effects compared to tricyclic antidepressants. They are relatively safer in overdoses. However they might lead to gastric irritation, nausia, vomitting, headache, increased anxiety and sexual dysfunction. 33

34. Pharmacologicalmanagement of unipolaraffective disorder Specific serotonin reuptake inhibitors: They cause decreased arousal, drive and difficulty reaching orgasm. These side effects might lead to noncompliance. The initial increased anxiety might lead to suicide. 34

35. Pharmacologicalmanagement of unipolaraffective disorder Monoamine oxidase inhibitors MAOIs : They are used for atypical depression with reversed biological symptoms as increased appetite and weight. It is recommended by NICE for those who do not respond to SSRIs. The ireversibleMAOIs have serious interaction with drugs and food containing tyramine. 35

36. Pharmacologicalmanagement of unipolaraffective disorder Monoamine oxidase inhibitors MAOIs : The reversible MAOIs as Meclobemide has less risk of interaction but therapeutically less effective. Those drugs lead to postural hypotension , overstimulation, sexual dysfunction, weight gain and possibly addiction. 36

37. Pharmacologicalmanagement of unipolaraffective disorder Serotonin and noradrenaline reuptake inhibitors SNRIs: Venlafaxine and duloxetene. Venlafaxine is more potent than SSRIs and recommended by NICE for severely depressed patients with monitoring the blood pressure. Doluxetene is not as potent as Venlafaxine and it might lead to initial nausea. Both drugs lead to nausea, hypertension, increased anxiety and sexual dysfunction. 37

38. Pharmacologicalmanagement of unipolaraffective disorder Other antidepressants: reboxetene: is selective noradrenaline reuptake inhibitor. It has anticholinergic side effects and sexual dysfunction. Neverthelss it is well tolerated but evidence of its effectiveness is scarce. mirtazepine: is α 2 adrenoceptor antagonist. It cause sedation and weight gain. Therefore it liked by patients with insomnia and disliked by obese patients. 38

39. Pharmacologicalmanagement of unipolaraffective disorder Other antidepressants: Mianserine is a tetracyclic drug and is α2 adrenoceptor antagonist. It is less popular now because of agranulocytosis. 39

40. Pharmacologicalmanagement of unipolaraffective disorder Treatment resistant depression: The possibilities are noncompliance, underlying physical illness as thyroid and cortisol. Bipolar disorder should be ruled out. Depression with psychosis needs adding antipsychotics. Depression with obsessional symptoms must be treated with SSRIs or clomipramine. 40

41. Pharmacologicalmanagement of unipolaraffective disorder Treatment resistant depression: Augmetation therapy: Antidep and psychtherapy Antidep and atypical antipsychotic Antidep and thyroid hormone 41

42. Pharmacologicalmanagement of bipolaraffective disorder The principles in treatment of bipolar disorders include psychoeducation, proprer monitoring, supporting carers, invlovement of carers and effective psychotherapy. R Hamish McAllister-WilliamsI Nicol Ferrier PSYCHIATR Y 8:4 113 © 2009 Elsevier Ltd. 42

43. Pharmacologicalmanagement of bipolaraffective disorder Mood stabilizers: Lithium : it is an antimanic and used prophylactic ally for bipolar disorder. It requires careful and continuous monitoring to avoid toxicity. Side effects include anorexia, metallic taste and diarrhea, polyuria and nephrogenic diabetes incipidus, tremor, weakness, cardiac toxicity, goitre and teratogenic effect. 43

44. Pharmacologicalmanagement of bipolaraffective disorder Mood stabilizers: Carbamazepine: it is used as an antimanic drug and for prevention of affective psychosis. However, its popularity has declined because its efficacy decreases with time as it is liver enzyme inducer and induces its own metabolism. It reduces the effectiveness of other anticonvulsants and contraceptives. It causes sedation, ataxia and diplopia. The serious toxic effects is Steven Johnson's syndrome. 44

45. Pharmacologicalmanagement of bipolaraffective disorder Mood stabilizers: Valproate:it is antimanic and has been used prophylatically but the evidence is not strong for its action. Side effects include gastric irritation, nausia, increased appetite, weight gain, tremor and thrombocytopenia. It could cause alopacia and hepatic damage too therefore it should not be used in patients with active liver disease. 45

46. Pharmacologicalmanagement of bipolaraffective disorder Mood stabilizers: Lamotrigine: Is an antiepileptic in complex partial and generalized tonic clonic fits. It is used for treatment of mania, depression, rapid cycling bipolar II disorder. Side effects: Headache, sedation, ataxia, diplopia, nausia 46

47. Pharmacologicalmanagement of bipolaraffective disorder Mood stabilizers: Lamotrigine: Other side effects include rash and Stevens Johnson’s syndrome. It does not induce liver enzyme p 450 and has no effect on psychotropic medication. 47

48. Pharmacologicalmanagement of bipolaraffective disorder Antipsychotics Atypical antipsychotics as olanzepine, resperidone, quetiepine and aripiprazole are effective as antimanic drugs in acute cases and prophylactically in bipolar disorder. They are useful in maintenance therapy. Olanzepine and aripiprazole are effective as continuation therapy after acute treatment. 48

49. Pharmacologicalmanagement of bipolaraffective disorder Antipsychotics The possibility of producing extrapyramidal side effects is less than typicals but weight gain and metabolic syndrome is a strong limiting factor for their use. 49

50. Pharmacologicalmanagement of bipolaraffective disorder Antidepressants Are used for depression but not prophylactically especially when there is risk of switching to mania. They could be combined with a mood stabilizer to avoid that risk. 50

51. Your attention and patience is appreciated 51