PM3PY2 Depression & Bipolar Disorder 2024-25 PDF

School of Pharmacy This session is being recorded. For more information see the Learning Capture Student Essentials page: https://bit.ly/yujaessentials If you have any concerns, please speak to your...

School of Pharmacy This session is being recorded. For more information see the Learning Capture Student Essentials page: https://bit.ly/yujaessentials If you have any concerns, please speak to your session lead. PM3PY2: Depression & Bipolar disorder Dr Angela Bithell [email protected] 2024-25 Trigger Warning: this session contains content on 1 mental health disorders, including associated suicide risk Copyright University of Reading Learning Outcomes By the end of this session you should be able to: Understand what depression is and distinguish between types of depression (including severity and e.g. major depression versus bipolar disorder) Summarise epidemiology and aetiology of affective disorders Explain treatment strategies, limitations, side-effects and risks for different types of depressive disorders Discuss how HCPs can help advise and decide with patients on treatment options and associated advice on treatment implementation Links with other PM3PY2 CNS & Mental Health topics (epilepsy, schizophrenia…) and upcoming workshop with Lee Karim (refer to relevant workbooks) 2 Mood and Affect Depression and mania are mood disorders (affective disorders) In psychiatric terms: Affect: an objective description of a person’s emotional behaviour Mood: an individual’s prevailing subjective emotional state Thus, mood disorders include illnesses with abnormally high or low mood, i.e. mania and depression. Mood disorders broadly include: Depression including its variants, bipolar disorder, dysthymia (subthreshold depression), cyclothymia… Often similarities and co-morbidity, also with anxiety 3 Classifying Mood/Affective Disorders Typically based upon assessments of: Severity Presence or absence of physical (somatic/biological) features Presence or absence of psychotic features Course (duration and recurrence) Subjective Presence or absence of intervening manic phases Criteria used to diagnose: UK: ICD-11/DSM-5 4 What is Depression? Depressed mood is a normal part of life Sadness and melancholy are normal responses to many everyday occurrences and will remit spontaneously Definition of clinical depression relies upon an understanding of what a normal response to a given situation should be Symptoms can be emotional, behavioural, physical and thought- based Depressed mood and/or loss pleasure in activities are central to depression 5 Depression: Epidemiology Represents large percentage of all psychiatric morbidity Many people will experience a depressive episode at some point and risk of recurrence is high Of these, 20%+ will develop chronic depressive illness Major depression affects ~5% of the adult population worldwide One of the leading causes of disability Women are more likely than men to experience depressive illness Prevalence increases with age Commonly presents with other psychiatric morbidity Wide range of other risk factors Increased risk of suicide, particularly in severe cases 6 Depression: Aetiology Complex and multifactorial: Biopsychosocial model (more with Lee Karim in workshop) Brain regional changes: – Regions important for mood and other functions linked to depression Genes and environment: – Family history is common in depression – Genetic and/or environmental components – Temperament/personality Medical conditions and medications (as well as substance misuse) Biochemical: – Reserpine (anti-hypertensive) a non-specific central amine depleter was reported to cause depression - controversial and has been disputed. Other drugs can cause depression (e.g. isotretinoin, interferon alpha) – Tricyclic anti-depressants prevent amine reuptake – Monoamine oxidase inhibitors act as effective antidepressants – Above evidence supports an ‘amine deficiency theory’ of depression, specifically 5- HT (serotonin) but not the only theory – AND there are no reliable metabolic or biochemical markers for depression 7 Monoamine Neurotransmission Noradrenaline (norepinephrine, NA, NE): Energy, concentration, memory, fight or flight NT Autoreceptors Serotonin (5- hydroxytryptamine, 5-HT): Mood, impulse control, cognition, appetite Dopamine: Reward, pleasure, Can be therapeutically targeted motivation, alertness, appetite Diagnosis of Depression Two main diagnostic criteria scales are used in diagnosis: DSM-V and ICD-11. [NICE guidance is based on these two sets of criteria – see later] Patient must exhibit at least one key (core) symptoms: low mood and/or loss interest/pleasure and symptoms should have been present for most of the time, most days for at least 2 weeks accompanied by other specific symptoms Not consistent with previous behaviour/personality and not secondary to other treatment Depression questionnaires such as the Beck Depression Inventory II (BDI-II), Patient Health Questionnaire 9 (PHQ-9) or Hospital Anxiety and Depression scale (HADS) can be to aid the diagnosis, assess symptom severity, functioning (and also to assess treatment effects) – valid in primary care. Hamilton Depression Rating Scale (HAMD) is also used. For example, PHQ-9 is based on DSM-5 and scores each criterion out of 3 – to maximum of 27 Need assess severity of symptoms But it’s all subjective 9 Diagnosis of Depression: NICE From current NICE guidance, HCPs need to: be alert to possible depression (particularly in people with a past history of depression or a chronic physical health problem with associated functional impairment) and consider asking people who may have depression two questions, specifically: During the last month, have you often been bothered by feeling down, depressed or hopeless? During the last month, have you often been bothered by having little interest or pleasure in doing things? If patients answer yes to either of these, a HCP qualified to perform a mental health assessment for the patient should do so (or refer if necessary), preferably using a validated measure to do so Current ICD-11 or Current DSM-5 Depression questionnaires can also be used in conjunction (e.g. HADS, BDI-II and PHQ-9) 10 ICD-11 and DSV-5 Comparison DSM-5 ICD-11 Depressed mood most of the day, nearly every day Depressed mood Marked diminished interest or pleasure in all or almost Diminished interest or pleasure in activities all activities most of the day, nearly every day Fatigue / loss of energy nearly every day Reduced energy or fatigue Hopelessness about the future Feelings of worthlessness or excessive or inappropriate guilt nearly every day Beliefs of low self-worth or excessive or inappropriate guilt Recurrent thoughts of death, recurrent suicidal ideation Recurrent thoughts of death or suicidal ideation or without a specific plan or a suicide attempt or a specific evidence of attempted suicide plan for committing suicide Diminished ability to think or concentrate or Reduced ability to concentrate and sustain attention indecisiveness, nearly every day or marked indecisiveness Psychomotor agitation or retardation Psychomotor agitation or retardation Insomnia or hypersomnia nearly every day Significantly disrupted sleep or excessive sleep Significant weight loss or gain or increase/decrease in Significant changes in appetite or weight appetite nearly every day DSM-V requires at least 5 out of 9 symptoms during same 2-week period with at least one core symptom ICD-11 at least one core symptom most of the day nearly every day for at least 2 weeks plus other symptoms11 such as those listed Severity of Depression: Previous Guidance Severity DSM-IV Major Depression ICD-10 Depressive Episode Sub-threshold Sub-threshold 2+, Flight of ideas or racing thoughts > Distractibility, poor concentration > Increased libido, disinhibition, and sexual indiscretions > Extravagant or impractical plans (for example business investments, spending sprees) > Psychotic symptoms: delusions (usually grandiose) or hallucinations (usually voices) > Diagnosis of a manic episode requires symptoms of mania lasting for at least 7 days which usually begin abruptly Hypomania is suggested by symptoms of mania that are not severe enough to cause marked impairment in social or occupational functioning, and the absence of psychotic features. > Diagnosis of a hypomanic episode requires symptoms to last for at least 4 days 29 Bipolar Disorder Identification 2 From NICE guidance continued: A mixed episode is suggested by a mixture, or rapid alternation (usually within a few hours), of manic/hypomanic and depressive symptoms. Depression is suggested by feelings of persistent sadness or low mood, loss of interest or pleasure, and low energy. Detection of bipolar disorder in people presenting with depressive symptoms may be improved by asking about a history of overactive, disinhibited behaviour lasting 4 days or more. The following questions may be useful: >'Do you currently (or have you in the past) experienced mood that is higher than normal, or do you feel much more irritable than usual, and have others noticed?' >'At the same time, do you have increased energy levels so that you are much more active or do not need as much sleep?’ These are based on expert opinions in e.g. DSM-V, ICD11 and other sources. Definitive diagnosis should be made via referral to specialist mental health services For full details see: BPD diagnosis NICE CKS 30 Management of BPD No known cause though some evidence of genetic/environmental links (70% concordance in identical twins). Strong genetic component. Aims of treatment: Control manic and depressive attacks Minimise recurrence and stabilise mood Control manic attacks typically with sedative anti-psychotics (atypicals) Prophylaxis for long-term treatment including mood stabilising drugs and psychological interventions (e.g. CBT). Mood stabilisers include: Lithium (common, long-term mood stabiliser but not immediately effective) Anticonvulsants, particularly Sodium valproate* (can help manage manic phases) Prophylaxis may also include: Other anticonvulsants used such as lamotrigine and carbamazepine Some atypical antipsychotics e.g. olanzapine or quetiapine Antidepressants not typically used or if used are in combination Benzodiazepines may be used short-term for mania (for MoA, Lecture 3) 31 Treatments for Mania and BPD: Lithium (carbonate) for acute mania or bipolar disorder and BPD prophylaxis BUT – very narrow therapeutic window, needs careful monitoring Blood monitoring – typically 0.6-0.8mmol/L (may have therapeutic effect at 0.4 or may need up to 1.0 Toxic at >1.5mmol/L but can have toxicity at lower (therapeutic) doses Sustained release formulations help avoid high peak plasma concentrations Takes 2-3 weeks to have effect Many side effects can include renal, endocrine, cardiac, neurological – reduced by lowering dose Drug interactions can affect levels (NSAID, diuretics, ACE inhibitors) MoA not fully understood, may include neuroprotection, modulation of neurotransmission, inhibition of GSK-3B or reduction of Inositol MONITOR thyroid and kidney function (and check CVS, renal and thyroid before commencing) Dr Tamagnini *sometimes used for depression to augment treatment with antidepressants in very severe cases Treatments for Mania and BPD 2: Antipsychotics (Atypicals, D2 antagonists and other mechanisms/targets) Can give control of mania and some help to prevent relapse/mood stabiliser Commonly atypicals such as olanzapine, quetiapine, risperidone (haloperidol is first generation/typical). Common side effects such as weight gain, sedation, hyperglycemia, anticholinergic). Other 2nd gen. atypicals may be used in mania and/or BPD e.g., aripiprazole (treatment mania and prevention recurrence) or asenapine (sublingual tablet, mod-sev manic episodes) – e.g., less risk weight gain and low anticholinergic effects Antiepileptic/anticonvulsants MoA not fully understood. Typically Na+ channel blockers that decrease AP firing (also putative action on other NT signalling) Valproate* – mania and prophylaxis of bipolar disorder (possible effects at voltage-gated sodium channels, GABA signalling, and others) Carbamazepine – prophylaxis of bipolar patients unresponsive to lithium, may be used for mania Lamotrigine – prophylaxis of bipolar disorder (and depression, not mania) Significant cognitive side effects *Dr Tamagnini *not women of child-bearing potential/pregnant (teratogen). If necessary, require Pregnancy Management of BPD 2 Primary care versus secondary care Initial mania treatment usually in secondary care (or in primary care with advice from specialist): options include atypical antipsychotics such as olanzapine, quetiapine, risperidone, or (typical) haloperidol Baseline monitoring and subsequent monitoring depending on treatment* If ineffective a second may be tried before adding lithium or sodium valproate (if lithium is unsuitable) If already taking antidepressants usually tapered and discontinued For depression in this period treatment options include e.g. Quetiapine alone, or Fluoxetine + olanzapine, or Olanzapine alone, or Lamotrigine alone Four weeks after resolution of acute episode establish long-term plan. Can include staying on current mania treatment or e.g. lithium (common) to prevent relapse with/without second agent Specific psychological therapy may also be offered If stable, a patient treated in secondary care may continue management in primary care (usually after at least 12 months) 34 Learning outcomes - Recap By the end of this session you should be able to: Understand what depression is and distinguish between types of depression (including severity and e.g. major depression versus bipolar disorder) Summarise epidemiology and aetiology of affective disorders Explain treatment strategies, limitations, side-effects and risks for different types of depressive disorders Discuss how HCPs can help advise and decide with patients on treatment options and associated advice on treatment implementation Links with other PM3B CNS & Mental Health topics (epilepsy, schizophrenia…) 35 Reference Material PM3PY2 Reading list books in the general “Nervous system’ and ‘Neurological disorders and mental health’ sections, including: ‘Fundamentals of clinical psychopharmacology’ (4th Edition, 2016, ed. Anderson & McAllister-Williams). Chapters 3-6 & 11 The Human Nervous System, ed. Mai & Paxinos, 2012. Sections III-VI 36  Mechanisms of Action ADs DAT 5H SSRIs inhibit SERT, some T 2C SERT SERT SERT differences may reflect SSRIs Fluoxetine Sertraline individual properties s SNRIs inhibit both SERT and NET, duloxetine NET inhibition SERT SERT > than venlafaxine Venlafaxine Duloxetine NRI NRIs inhibit NET (e.g., NE T NE T NE reboxetine) T Mirtazapine (NaSSa) 5H T 2C 5H T antagonist H1, a2 and several SER T 2C 5HT 2A H1 5HT 2A H1 5HT receptors Mirtazapine 5HT 3 Trazodone Trazodone (SARI) action at 5HT, a2 a1 H1, a1 and SERT 5H H1 T 2C 5HT TCAs almost all inhibit SERT, SERT 2A s TCAs NET, H1 (and H2), a1, mACh Note: Dose can be (M), 5HT (and agonists s1 & 2 NE and sodium channel blockers) M important for T 1 a1 which  Mechanisms of Action Typical antipsychotics (e.g., haloperidol) block D2 receptor Most atypicals (2nd gen) have additional 5HT, H1 and adrenergic actions in addition to D2 (some also act at other D receptors). Differences between individual agents Some (e.g., clozapine and olanzapine and to a lesser extent quetiapine) also block M1/M3 (mACh) MOAIs: block action MOA – thus block breakdown of monoamines Anticonvulsants: typically sodium channel blockers Pregabalin: inhibits a2d subunit voltage-gated calcium channels (sim. gabapentin) Benzodiazepines: positive modulators GABAAR (increase action) Buspirone hydrochloride: main action as 5-HT1A receptor partial agonist Image Top (A and B, antipsychotics, Grinchii & Dremencov 2020. Int. J. Mol. Sci., 21(24), 9532 CC-BY 4.0