1. DEPRESSION AND ANXIETY Hope and Amy

2. DEPRESSION LEARNING OUTCOMES  Define the main symptoms aetiology and neurological basis for depression  Describe the pharmacological and interventional approaches used in the treatment of depression  Describe the classes and mechanisms of action of the most common antidepressants  Describe the problem and side-effects associated with antidepressant drugs

3. MOOD AND AFFECT  Define mood:  A patient’s sustained, subjectively experienced emotional state over a period of time.  Define affect:  The outward manifestation of the internal emotions.

4. ASSESSMENT AND DIAGNOSIS OF DEPRESSION  Key to diagnosing depression is the history.  “In the past month have you…”  Felt down, depressed or hopeless?  Found that you no longer enjoy, or find little pleasure in life?  Been feeling overly tired?  ALWAYS ASSESS SUICIDE RISK

5. LIST SYMPTOMS OF DEPRESSION…

6. SYMPTOMS For a diagnosis of depression, according to DSM-IV, 5 of the 9 following symptoms must be continuously present for the minimum of two week period: 1. Persistent sadness or low mood. 2. Marked loss of interest/pleasure - anhedonia 3. Disturbed sleep – increased or decreased 4. Fatigue or loss of energy 5. Agitation/slowing of movements/retardation. 6. Poor concentration. 7. Feelings of worthlessness/excessive guilt. 8. Suicidal thoughts or acts – red flag. 9. Weight of appetite loss

7. DEAD SWAMP  DEAD SWAMP – depression history taking made easy!  D – Depressions  E – Energy levels  A – Anhedonia  D – Death – thoughts about death and self harm.  S – Sleep pattern  W – Worthlessness, guilt  A – Appetite  M – Mental function (concentration/cognition)  P – psychomotor agitation and retardation

8. ‘MAIN SYMPTOMS, AETIOLOGY AND NEUROLOGICAL BASIS OF DEPRESSION’  Types of depression:  Mild - Few symptoms in excess of the 5 required to make the diagnosis. Symptoms only results in minor functional impairment.  Moderate – Symptoms between ‘mild’ and ‘severe’.  Severe – Most symptoms, and they markedly interfere with functioning. Can occur with or without psychotic symptoms.  Patterns  Unipolar – dysthymia (neurotic/chronic depression –less severe but longer lasting symptoms), melancholia, atypical depression  Bipolar – bipolar disorder, cyclothymia (cycling moods)

9. AETIOLOGY  Theories:  Monoamine  Neurohormones  Immune  Circadian  Psychological factors

10. MONOAMINE THEORY  Suggests that depression is due to a shortage of noradrenaline, serotonin and possibly dopamine.  NA: locus coeruleus  5HT: raphe nuclei in medulla.  DA: substantia nigra and ventral tegmental area.  Suggests why antidepressants are effective: as each class makes more monoamine molecules available in the synaptic cleft.

11. NEUROHORMONES  CORTISOL  Suggested that depression could be to do with dysregulation of the HPA axis. IMMUNE  Inflammatory responses induce HPA activity and can also induce depressive behaviour.

12. PSYCHOLOGICAL FACTORS  (Endogenous rhythm that cycles every 24 hours).  Circadian rhythms can help tell acute and chronic depression apart.  Changes in circadian rhythm could cause depression. CIRCADIAN RHYTHMS  Vulnerability factors in women:  Marital separation  Job loss  Having three or more children at home under the age of 14  Not working outside the home  Lacking a confiding relationship  Loss of a mother before the age of 11

13. WHAT NEUROLOGICAL CHANGES CAN BE SEEN IN DEPRESSION?  Circuitry  Decreased activity in prefrontal cortex and hippocampus (‘seat of good judgement’ and memory).  Increased activity in amygdala and hypothalamus (fear, memory and stress)  Neurogenesis  Decreased arborisation  Decreased synapses

14. PHARMACOLOGY

15. TCAS  What are TCAs?  Tricyclic antidepressants  How do they work? (5)  5HT reuptake inhibitor  NA reuptake inhibitor  A1 – adrenoceptor antagonist  H1 receptor antagonist  M1 receptor antagonist – side effects

16. TCAS  Give an example of a TCA  Amitriptylline  Side effects.  Dry mouth  Blurred vision  Constipation  Urinary retention  Tachycardia  Postural hypotension

17. SSRIS  What is an SSRI?  Selective serotonin reuptake inhibitor.  Give 4 examples of SSRIs?  Paroxetine  Fluoxetine (prozac)  Citalopram  Sertraline

18. SSRIS  How do they work?  Inhibit the reuptake of serotonin from the synaptic cleft, allowing it to exert its effect on the post-synaptic membrane for longer.  List some side effects of SSRIs:  Nausea  Sleep disorders  Sexual dysfunction  Drug interactions: SEROTONIN SYNDROME!

19. WHAT IS SEROTONIN SYNDROME?  Severe condition caused by too much serotonin, either due to large doses of one drug or combinations.  Caused by: SSRIs/TCAs  Tramadol  Cocaine/MDMA  Symptoms: increased heart rate, shivering, sweating, dilated pupils, myoclonus, high fever, seizures. DEATH.

20. MAOIS  What are MAOIs?  Monoamine oxidase inhibitors  How do they work?  Increase noradrenaline/serotonin levels by inhibiting their breakdown in the synaptic cleft.  Give an example:  Phenelzine  Give some side effects/important drug interactions:  MUST NOT be used with SSRIs or TCAs – causes an autonomic overload – increases levels of neurotransmitters in the cleft and also inhibits the ability to break them down. Cheese reaction: tyramine from cheese increase the release of noradrenaline and MAOIs cannot break it down.

21. ADRENOCEPTOR ANTAGONISTS  Release of monoamines is modulated by  adrenoceptors.   1 adrenoceptors - increase – agonists - speed up transmission.   1 adrenoceptors increase monoamine release into the synapse. SO agonists increase this effect.   2 adrenoceptors – decrease – antagonists - disinhibition– eg Mirtazapine.  Some evidence shows increased  2 adrenoceptors in depressed patients – increased inhibition.   2 adrenoceptors inhibit monoamine release from presynaptic neuron, therefore antagonists prevent this inhibition.

22. ATYPICAL ANTIDEPRESSANTS  NRIs – noradrenaline reuptake inhibitors – work the same as SSRIs  Reboxetine  SNRIs – serotonin – noradrenaline reuptake inhibitors  Venlafaxine.  5HT partial agonists – increase levels of serotonin.  Buspirone

23. LITHIUM  How does it work?  We don’t know!  Either: Acts to reduce g-protein function and inhibits IP pathway signalling, or suppresses gene function, or increases neurogenesis.  Useful in mania and bipolar affective disorder – used as a last resort in depression.  Adverse effects: narrow therapeutic window - fine line between therapeutic and toxic.

24. LIST 6 NON-PHARMACOLOGICAL TREATMENTS FOR DEPRESSION:  Exercise  Light therapy  Agomelatine – melatonin agonist.  CBT  Transcranial magnetic stimulation  ECT

25. IF THERE’S TIME…..

26. ANXIETY LEARNING OBJECTIVES  Describe the key features of GAD  Understand the different treatment approaches  Understand the transactional definition of stress  Describe the transactional model of stress.

27. STRESS  Effects of stress:  ‘Stress not only increases risk of illness among the healthy but also impedes recovery/worsens prognosis among the ill’.

28. DESCRIBE THE STAGES OF GENERAL ADAPTATION SYNDROME:  Physiological response to stress.  Stages:  Alarm – fight or flight  Resistance – conservation response to maintain homeostasis.  Exhaustion – immune failure and occurrence of disease.

29. WHAT IS GAD?  Generalised anxiety disorder.  What defines GAD?  Excessive uncontrollable and often irrational worry more days than not for at least 6 months.  List psychological and physical symptoms:  Psychological  Worry, interrupted sleep, poor concentration, increased sensitivity to noise.  Physical  Sweating, dry mouth, urinary frequency, hyperventilation, palpitations.

30. WHAT ARE 4 DIFFERENT TREATMENT APPROACHES TO GAD?  Pharmacological  Mindfulness  CBT  Thought diary

31. TRANSACTIONAL MODEL OF STRESS URGH.  How a stressor is appraised by an individual.  Can help stressed people by teaching them to interpret stressors differently. ‘Stress is what you make of it!’

32. TORTOISE WITH HAT.