Mood Disorders

1. Mood Disorders - Major depressive Disorder - Bipolar Disorders - Dysthymia - Cyclothymia - Other mood disorders

2. I- Major depression - Primary disturbance in mood - Syndromes rather than disease - Occur in cyclic fashion - Lost sense of control

3. DSM IV Classification of mood disorders - Major depressive disorder ( unipolar depression ) = 2 weeks - Hypomania = 4 days - Bipolar I (Mania for 1 week, alternating episodes of Mania+ Mania, Mania+ MDD) - Bipolar II( Hypomania+ MDD) - Mixed episode = 1 week

4. Epidemiology A-Prevalence - Life time prevalence MDD 10-15% in women Bipolar I = 0.4-1.6% 5-12% in men Bipolar II =0.5% B- Sex In MDD -Women : Men = 2:1 Why? Child birth, hormonal differences, psychosocial stressors In Bipolar - Women = men C- Mean age of onset Bipolar I = 30 years MDD = 40 years

5. D- Marital Status More in single, divorced, separated, poor interpersonal relations E-Socioeconomic Status No correlation for MDD, bipolar more in high SES Depression more in rural areas

6. Etiology A- Biological Factors 1- Biogenic amines ( levels in blood, urine, CSF) Heterogeneous dysregulation of the biogenic amines Low nor epinephrine, Serotonin in depression, Low dopamine in depression and high in mania Others, GABA, Glutamate 2- Neuroendocrinal dysregulation - Adrenal Axis ( Non suppression of dexamethasone suppression test) - Thyroid Axis Antithyroid antibodies, low thyroid hormones, development of rapid cycler

7. 3- Sleep EEG abnormalities Delayed sleep onset , short rapid eye movement( REM ) Latency, Increased duration of 1st REM period, abnormal Delta sleep 4- Neuroimmune dysregulation 5- Brain imaging studies Enlarged ventricles and small frontal lobes, Diminished cerebral blood flow

8. 6- Genetic factors Genetic evidence through family studies, adoption studies, twin studies. Molecular biology: involvement of chromosome;5,11,18,X. B- Psychosocial factors - Life stressor commonly precede the occurrence of first MDD and bipolar disorder. - Life events common in past history of patients : Loss of parent before the age of11 years, loss of spouse , unemployment.

9. C- Personality factors - OCD, histrionic, borderline predict depression - Dysthymia and cyclothymia predict bipolar D- Psychodynamic factors - In depression: damaged early attachment and traumatic separation in childhood - In Mania: defense against underlying depression E- Cognitive theory Aaron Beck gave triad: depressed patient have negative view of self, world and future.

10. Major depression ( clinical picture) 1- Psychological symptoms A- Depressed mood and sadness ( usually there is diurnal variation) B- Loss of interest and lack of enjoyment (anhedonia) C- Sense of emptiness, helplessness, hopelessness, worthlessness, pessimism, death wishes, suicidal thoughts, loss of self esteem, self blame and guilt D- Psychotic symptoms in severe cases and are going with low mood Delusions of guilt, nihilism, poverty, hypochondrias is and somatic delusions. Hallucinations: auditory, visual.

11. 2- Physiological symptoms ( somatic symptoms) a- Diminished appetite B- Weight loss C- loss of sexual desire D- Sleep disturbance: insomnia, early morning awakening, interrupted sleep E- Pains ( Headache, back pain) F- Digestive upsets and loss of appetite Sometimes atypical symptoms ( increased appetite and hypersomnia

12. 3- Behavioral symptoms A- Negligence of self care B- Social withdrawal, suicidal attempts 4- Motor and cognitive functions A- Difficulty in attention and concentration B- Slow thinking C- Psychomotor retardation or agitation D- Negative view of self, world and future 5- impaired social and occupational functioning

13. DSM IV criteria of Major Depressive episode - Five or more symptoms present in the past 2 weeks with at least one either 1 or 2 1- Depressed mood and sadness 2- Loss of interest or pleasure 3- change in appetite 4- Insomnia or hypersomnia 5- Psychomotor retardation or agitation 6- Fatigue, loss of energy, or sexual problems 7-Feeling of worthlessness or excessive guilt 8- Decreased ability to think 9- Recurrent thoughts of death, suicidal ideas, or attempts

14. - Specify: A- Mild, moderate, severe B-With or without psychotic features (mood congruent/ incongruent) C- With ; 1-Atypical features - Mood reactivity, weight gain, hypersomnia, interpersonal rejection 2-Melancholic features Severe anhedonia, weight loss, early morning awakening, guilt over trivial events, suicide

15. 3- Seasonal pattern Regularly occurring every winter or fall 4- Catatonic Features Motoric immobility, excessive motor activity, negativism, mutism, posturing, stereotyped movement, echolalia, echopraxia 5- Postpartum Within 4 weeks postpartum

16. Differential diagnosis 1-Medical disorders -Substance induced mood ( abuse as sedatives , hypnotics, opoiods, phencyclidine, or prescribed as contraceptive pills, corticosteroids, reserpine, cimetidine, alpha methyldopa, propranolol, amphetamines ) -Thyroid, diabetes, adrenal diseases, Rhematoid arthritis,SLE cancer lung,git -AIDS 2-Neurological ( Parkinsonism, CVS, epilepsy, brain tumors) 3- Other mood disorders 4- Bereavement 5- Other mental disorders - Personality disorders - Schizophrenia - Dementia

17. Management of MDD A) Acute phase treatment = induction of remission( 4-6 weeks) 1- MDD (mild, moderate) Pharmacotherapy +Psychotherapy 2- Severe without psychotic features Pharmacotherapy+ Psychotherapy+ ECT 3- Severe with psychotic features Pharmacotherapy +ECT + Antipsychotic 5- MDD and catatonic Pharmacotherapy +ECT + Antipsychotic + BDZ 6- MDD in bipolar Mood stabilizer + antidepressant

18. Most depressive illnesses can be managed in primary care setting, especially those with mild and moderate symptoms Refer to psychiatrist if: suicidal risk is high, Severe depression or psychotic depression, non response to treatment I- Hospitalization 1- Suicide or homicide 2- To be sure of the diagnosis 3- Progressive symptoms and severe retardation 4- No social support 5- Catatonic 6- Psychotic depression 7- Refusal of treatment and food 8- Impaired insight

19. II- Electroconvulsive therapy (ECT ) 1- Resistant pharmacotherapy 2- Condition need rapid improvement 3- Patient can't tolerate drugs 4- Catatonic 5- severe cases 6- suicidal symptoms

20. III- Pharmacotherapy A- Choice of drug - Patient preference - Family history - Adverse effect - Cost of the drug - Clinician experience - Pattern of symptoms B- Strategies and dose - Monotherapy ( TCA or SSRI ) Others ( MAOI, SNRI, Trazodone, Mirtazapine ) - Duration of each trial = 4-6 weeks - If failed , check compliance, dose, drug level, and diagnosis - Substitute, combine, augment with lithium, carbamazepine, L- thyroxine , or consider ECT

21. 1- Tricyclic antidepressants (TCA ) - Amitryptyline( Tryptizole) = 75-150 mg - Imipramine( Tofranil) = 75-150 mg Side effects - Cardio toxic - Sedation, postural hypotension - Weight gain - Anti cholinergic - Neurological 2- Selective Serotonin Reuptake Inhibitor (SSRI ) Escitalopram( Cipralex) = 20-60 mg Fluoxetine( Prozac) 20-60 mg Sertraline ( Lustral) = 50-200 mg Fluvoxamine( Faverine) = 50-300 mg Paroxetine( Seroxate) 20 mg

22. Side effects - GIT upset , Insomnia, agitation, headache, sexual - Serotonin syndrome especially in combination ( Abdominal pain, fever, sweating, and flushing ) 3- Others - Tetracyclic antidepressant as Maprotiline (ludiomil) = 150-300 mg - MAOI if atypical features ( used cautiously ) - SNRI as Venlafaxine ( Effexor)= 75-150 mg - Serotonin modulator as Trazodone( Trettico) = 150-600 mg - Bupropion ( wellabutrin) = 150 mg /day - Nor epinephrine Serotonin modulator as Mirtazapine (Remeron) = 30 mg

23. IV- Psychotherapy A- Cognitive therapy Goal; Alleviate episode and prevent recurrence Technique: help patient to develop alternative ,flexible, and positive ways of thinking B- Interpersonal therapy Based on the fact that problems in interpersonal relations precipitate depressive illness C- Behavioral therapy D- Family therapy E- patient education

24. B) Continuation Phase treatment - Aim : Prevent relapse - Duration: 6-8 months - Strategy: same treatment and same dose

25. C) Maintenance Phase - Aim: Prevent recurrence of symptoms - Indications: Severe, psychotic depression, positive family history, serious, or recurrent - Duration: If 2 episodes: interepisode duration - If more than 2 episodes: 5 years or for life - Strategy: Least effective dose

26. II- Dysthymia Dysthymic disorder Definition Is a chronic disorder characterized by the presence of depressed mood that lasts most of the day and is present almost continuously i.e Low grade depression, accentuation of depressive temperament Epidemiology - 5-6 % of all persons - Onset: childhood and adolescence - Sex = equal - More in unmarried people, low income - Coexist with MDD, medical illness, anxiety disorders especially panic, substance abuse and borderline personality disorder

27. Etiology As in depression Clinical features - 2 Years duration ( continuous ) Subjective > objective - Depressed mood - Habitual gloom, brooding, lack of joy, preoccupation with inadequacy - No severe disturbance in appetite, libido, psychomotor retardation DD - MDD - Minor depressive disorder Episodic, periods of euthymic - Double depression MDD on top of dysthymia, Poorer prognosis

28. Treatment I- Hospitalization Mostly not indicated except if marked affecting social life II- Consider thyroid disease III- Combine psychotherapy and pharmacotherapy A- Cognitive therapy i- Technique Teach patient new way of thinking ii- Replace faulty negative attitude about themselves, world and future

29. B- Behavioral therapy Goals: Increase activity, provide pleasant experience, and teach patient how to relax C- Interpersonal therapy Improve interpersonal relations to improve self esteem D- Family and group therapy

30. IV- Pharmacotherapy - Maximum dose - Duration: 8 weeks - Drug: bupropion, MAOI, TCA - If failed Augment with lithium

31. III) Other depressive disorders 1- Depressive disorder not otherwise specified A- Premenstrual dysphoric disorder B- Minor depressive disorder C- Recurrent brief depressive disorder D-Post psychotic depressive disorder of schizophrenia 2- Mixed anxiety depressive disorder 3- Atypical depression 4- Secondary depressive disorder - Mood disorder due to GMC - Substance induced mood disorder

32. 1-Premenstrual dysphoric disorder (Luteal phase dysphoric disorder ) Definition Syndrome characterized by mood, behavioral, and physical symptoms occurring at specific time during the menstrual cycles and resolves in-between cycles Epidemiology 40 % have symptoms 2-10 % have syndrome

33. Etiology 1- Hormonal changes Abnormal high estrogen: progesterone ratio 2- Biogenic amines affected by changes in hormones 3- Societal and personal issues about menstruation and womanhood

34. Clinical picture Presentation for 1 year A- Mood symptoms Depressed mood, anxiety, lability of affect, angry or irritable, increased interpersonal conflicts, sense of being out of control B- Behavioral changes Diminished usual activities, easy fatigability, change in sleep, appetite, and difficult in concentration C- Physical symptoms Breast tenderness, headache, joint pain , muscle pain, and sense of bloating ( wt gain ) Symptoms are severe to affect work, school, and social activities and relations

35. DD - If no intercycle relief of symptoms, consider other mood disorder If severe symptoms, exclude medical and surgical causes as endometriosis Treatment 1- Supportive psychotherapy 2- Mild antidepressant esp. Fluoxetine (has long half life) , and bezodiazepines esp. alprazolam 3- Vitamins

36. 2- Minor depressive disorder 2 weeks of mild symptoms than MDD Treatment, mainly psychotherapy 3- Recurrent brief depressive disorder Depressive disorder last from 2 days- 2 weeks Recurrent / month for 12 months, not related to menses Mostly +ve family history of mood disorder 4- Post psychotic depressive disorder MDD in residual phase of schizophrenia

37. 5- Secondary mood disorder A- Mood disorder due to general medical condition (GMC) - Persistence disturbance in mood ( depressed or elevated ) - Evidence ( history, examination, or lab of general medical condition ) - Absence of delirium - Significant impairment

38. B- Substance induced mood disorder - Persistence disturbance in mood ( depressed or elevated ) - Evidence ( history, examination, or lab of substance intake ) - Absence of delirium - Significant impairment Pharmacological causes of depression - Cardiac and antihypertensive drugs - Sedatives and hypnotics - Steroids and hormones - Stimulants and appetite suppressants - Analgesics

39. Pharmacological causes of mania - Amphetamines - Cocaine - Corticosteroids - Cyclosporine - Hallucinogens - Methylphenidate - Opiates and opioids - Phencyclidine

40. II- Bipolar disorders Episodes of both depression and mania (bipolar I) or hypomania (bipolar II) occur in separate episodes with a period of full or partial remission in between episodes Clinical picture 1- psychological Mood: elation, euphoria, and irritability Thinking: racing thoughts, flights of ideas, mood related psychotic symptoms e.g delusions of grandiosity and power Speech: hypertalkativness in a loud and rapid voice Judgment: impaired

41. 2- Behavioral - Hyperactivity, restlessness - Grandiose attitude and inflated self esteem - Increased sociability, aggression and excitement - Enthusiasm, multiple projects - Sexual and social disinhibition - Wearing bright colors, excessive cosmetics - Overspending of money 3- Physiological Full energy and lack of sense of exhaustion, decreased need for sleep, increased sexual activity, excessive eating

42. 4- Cognitive and psychomotor - Hyperactive - Psychomotor agitation - Distractability

43. DSM IV criteria of Manic episode 1- Elated, expansive, or irritable mood for 1 week - Three or more symptoms present in the past 1 week 2- Inflated self esteem or grandiosity 3- Decreases need for sleep 4- Hyper talkative 5- Flights of ideas 6- Distractability 7- Involvement in pleasurable activity

44. 8- Disinhibition 9- Impulsivity 10- Preoccupied by religious, sexual ideas or behaviors - Specify: A- mild, moderate, severe B-With or without psychotic features (mood congruent/ incongruent) C- With catatonic features, postpartum onset D- If recurrent; rapid cycler or not

45. Hypomania 4 days of mild manic symptoms not affecting function, but observed by others Mixed episode The patient meet the criteria for depression and mania every day for 1 week Bipolar with rapid cycler 4 episodes in 1 year

46. Treatment of Bipolar disorder A) Acute phase = 4-6 weeks I- Hospitalization ( as in MDD ) II- ECT - Catatonic excitement - Acute mania III- Pharmacotherapy Mood stabilizer + sedative + antipsychotic if with psychotic features IV- Psychotherapy Has no role, cognitive therapy may be used to prevent further attacks.

47. Approved mood stabilizers -Typical features: Lithium carbonate ( Comcolit) 400 mg tab, 2 tablet/ day divalproex( depakene chrono) 500 mg tab, 1-3 tablet/day, olanzapine( Zyprexa) -Atypical features (Dysphoric mania, mixed episode, rapid cycler ): Carbamazepine ( Tegretol)200 mg tab. 3-6 tablet/day, or Divalproex - Sedatives used: Benzodiazepines e.g Clonazepam( rivotril ), antipsychotics discontinued after 2-3 weeks - Antipsychotics( Chlorpromazine, haloperidol)

48. - Trial = 4-6 weeks If fail check drug, dose, diagnosis, compliance Substitute, or combine lithium + Divalproate - Drugs A- Lithium Dose = 800-1200 mg/day Serum level = 0.8-1.2 meq /l Side effects Renal dysfunction, poluria, tremors, hypothyroidism, Hypokalemia and ECG changes, Ebstein anomaly, Seizures B-Carbamazepine and Divalproex C- New antiepileptic: Lamotrogine and Gabapentin ( add on )

49. B) Continuation Phase = 6 months Strategy: Same dose of mood stabilizer, discontinue antipsychotic C) Maintenance phase If more than one episode, for 2 years

50. Cyclothymic disorder Definition Chronic ( 2 years ) fluctuating disturbance include periods of hypomania and depression in milder form than bipolar I, shorter duration than bipolar II Epidemiology Life time prevalence = 1 % Coexist with border line personality disorder, and substance abuse Clinical features - Presentation : marital difficulties, instability of interpersonal relations

51. - Changes in mood are irregular, abrupt sometimes occur within hours - Patient may be achiever if controlling his symptoms or may have professional and social difficulties Differential diagnosis - Substance abuse - Mood disorder due to general medical condition - Personality disorder - Bipolar II disorder

52. Treatment I- Pharmacotherapy - Mood stabilizer ( Lithium, carbamazepine, depakeme, clonazepam, gabapentin ) - Antidepressant used with cautious to avoid antidepressant induced hypomania II- Psychotherapy 1- Individual therapy Education to increase patient awareness to their condition and to help him to develop coping mechanism for their mood swings 2- Family and group therapy

53. Psychoeducation -