Anxiety and Depression Flashcards
What is the NHS definition of anxiety? When is a diagnosis made?
- “A feeling of unease; worry or fear, that can be mild or severe (chronic or acute”
- Diagnosis of anxiety made if:
> Anxiety occurs all the time.
What are the different types of anxiety?
- Panic disorder
- Obsessive compulsive disorder (OCD)
- Post-traumatic stress disorder (PTSD)
- Phobias; specific or social
- Generalised Anxiety Disorder (GAD)
What is Panic disorder? What symptoms is is characterised as?
- Intense and abrupt feeling of fear or discomfort
Symptoms:
1) Sudden temperature change
2) Chest pain/interruption to normal blood circulation; palpitations/tingling sensation
3) Nausea + dizziness
4) Overwhelming feelings
What is OCD? What are the characteristics of each part?
- A combination of obsessive thoughts and compulsive activity
Obsession:
- Unwanted/unpleasant thoughts that cause anxiety e.g. being burgled
Compulsive:
- Repetitive behaviour a person undertakes to relieve the unpleasant feeling
What is PTSD? What are its symptoms? Onset?
- Post-traumatic stress disorder; after experiencing a trauma e.g. serious accident, natural disaster, criminal assault, returning from war etc.
- Can develop immediately or years later
Symptoms:
- Insomnia
- Nightmares
- Flashbacks
- Isolation
What is Specific phobia?
Intense fear of something that in reality is of little or no actual danger.
What is Social phobia?
- Fear of social/performance situations, resulting from thoughts of negative judgement, embarrassment or humiliation
- Person ‘tolerates’ with dread, or avoids the situation
- Common with performers/actors etc
What is GAD?
> Generalised anxiety disorder Excessive, uncontrollable worry about everyday things such as: - Job - Finances - Health - Family - Chores - Car repairs - Late for appointments
- Intensity, duration and frequency of worry is disproportionate to the issue
- May occur w/other anxiety disorders, depressive disorders or substance abuse
- May also present w/physical symptoms e.g. difficulty sleeping, palpitations & tingling in hands
What are some potential causes of anxiety?
- Genetics? (no gene isolated, but familial history can predispose risk)
- Neurochemical/neurohormonal
- Environmental factors
- Substance abuse
What symptoms that can present as anxiety could be due to organic disease? Give examples.
SOB:
- Asthma
Palpitations, tachycardia:
- Heart disease
Palpitations, sweating, tremor:
- Hyperthyroidism
- Phaeochromocytoma (adrenal tumour)
Dizziness:
- Vestibular dysfunction (inner ear problem)
- Hypoglycaemia
Sweating:
- Menopause
What are the considerations that need to be made during assessment for anxiety?
- Mental health history
- Environmental stressors
- Medical and drug history
- Degree of distress and functional impairment (e.g. insomnia)
- Risk of suicide; doctor should outright ASK > refer
What is the aim of anxiety (e.g. GAD) management/treatment?
- Relieve symptoms
- Improve QoL
- Prevent relapse
What non-pharmacological treatments are there for anxiety (GAD)?
- CBT (NICE recommendation, evidence-based, whilst following are not:)
- Mediation and relaxation (complements pharmacological therapy)
- Mindfulness “stop and smell the roses”; appreciating what’s around you
- Exercise (complements pharmacological therapy)
How are autonomic symptoms (palpitations/tingling) managed in anxiety (GAD)?
β-adrenoceptor antagonists (propranolol)
- Reduces autonomic effect
- Used on PRN basis
- DO NOT withdraw abruptly; prevent rebound effects
What are the pharmacological options of treating anxiety (GAD)?
Selective serotonin reuptake inhibitor (SSRI):
- Serotonin (off-label treatment in GAD)
- Licensed; escitalopram and paroxetine
What are the options if there is no improvement of Patient A’s anxiety after 2 months treatment w/SSRI?
1) Increase dose if max. dose not yet achieved
2) Swap to another SSRI
3) Consider a serotonin-NA reuptake inhibitor (venlafaxine, duloxetine)
4) Consider anticonvulsant agent, pregabalin (last line due to large S/E profile; blocks Glu transmission)
What are the therapeutic properties of Benzodiazepines (BDZ)?
- Anxiolytic (appropriate for GAD)
- Sedative ‘minor tranquilisers’
- Muscle relaxant; central effects (e.g. used when intricate surgery required)
- Hypnotic (induces sleep)
- Anticonvulsant
- Amnesic
- Reduce aggression
- Treats alcohol withdrawal
What are the pharmacokinetic properties of BDZ?
- No enzyme induction; can monitor pharmacokinetic profile
- Metabolism through oxidation and conjugation (after getting to brain, like lorazepam)
- Oxidation reduced by agel effects may be prolonged in older patients (risk of toxicity if drug not metabolised; give lorazepam; metabolism through conjugation)
- Active metabolites
- Relatively safe in overdose
What are the disadvantages with BDZ use?
- Some tolerance (higher dose may be required)
- Dependence and withdrawal symptoms (2-3 weeks; use short-term)
What BDZs are suitable for GAD treatment? Are they first line?
Drugs with a short (1-10 hours) half-life: Hypnotics: - Temazepam - Nitrazepam - Zolpidem
Drugs with longer half-life (1-4 days): Anti-anxiety: - Diazepam - Chlordiazepoxide (alcohol withdrawal) - Lorazepam
> > > SSRIs first line; BDZs best avoided, but use restricted to 2-4 weeks.
What is the GABAa receptor complex? Why is it complex?
- Receptor complex for the inhibitory NT, GABA
- Pentameric structure w/Cl- pore in middle
- 5-sub-unts, each with a different binding site:
> Barbiturate (+ alcohol?)
> Picrotoxin (antagonist of GABA action)
> GABA site
> Steroid
> Benzodiazepines (and anaesthetics)
How do BDZs work?
- Occupy site on GABAa complex
- Increases affinity for GABA (conformational change of GABAa receptor complex)
- Thus greater flow of Cl- ions into neurone
- HYPERPOLARIZATION occurs; hence inhibitory action (and anxiolytic nature)
What are the risk factors for suicide?
- Own history of depression, suicide attempt
- Illness e.g. chronic pain syndrome (most common cause)
- Schizophrenia and dementia etc.
- Family history of depression
What is DSM-5, and what are the markers of depression?
- Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition
Core symptoms of depression (1+2):
1) Depressed mood; “Does not feel able to get back on track”
2) Loss of interest or pleasure “not attending rambling or yoga”
3) Fatigue; “Weary and lacking in energy during the day”
4) Feelings of worthlessness, guilt or inappropriate grief “husband’s death”
5) Recurrent thoughts of death or suicide/actual suicide attempts
6) Reduced ability to think or concentrate
7 Psychomotor agitation or retardation
8) Altered sleep “problems dropping off to sleep, early morning waking”
9) Significant weight change; “lost a lot of weight”
What are the categories of depression?
- Subthreshold
- Mild
- Moderate
- Severe
What is classified as subthreshold depression?
- At least 2 but less than 5 symptoms (as laid out by DSM-5)
- One ‘core’ symptom
What is classified as mild depression?
- Few but in excess of 5 symptoms
- Minor functional impairment
What is classified as moderate depression?
- Some marke symptoms
- Presence of functional impairment
What is classified as severe depression?
- Multiple symptoms
- Markedly interfere w/functioning (e.g. not sleeping/doing anything)
How much do genes or the environment contribute to severe and mild depression respectively?
- Severe; more influence from genes (familial component), minor environmental influence
- Mild; more influence from environment (e.g. death of a partner) than genes
What is bipolar disorder, when does it first present and what populations are more prone?
- Cycle between depressed mood and mania
- First episode observed before age 30, with a peak incidence between 15-19 years of age (early-onset)
- Increased incidence in ethnic minorities (in the UK)
Describe what the ‘depressed mood’ phase of bipolar disorder entails.
Period of at least two weeks with core symptoms accompanied by at least 4 other symptoms (DSM-5)
Describe what the ‘mania’ phase of bipolar disorder entails.
- Elevated mood
- Increased energy
- Incomprehensible speech
- Racing thoughts
- Poor concentration
“Hyperexcitability”
What is the process involved in diagnosing bipolar disorder?
- Eliminate misdiagnosis; differential diagnosis
- Confirmed by a specialist mental health professional (as bipolar treatment is complicated)
How is the acute phase (mania) of bipolar disorder treated?
Antipsychotics:
- Haloperidol
- Olanzapine
- Quetiapine
- Risperidone
> If ineffective, swap to another antipsychotic from above
> > If ineffective, add lithium (not favoured due to narrow therapeutic window, but used prophylactically for 60+ years) or sodium valproate (anti-convulsant)
What is involved in maintenance therapy of bipolar mania?
- Continue treatment as per acute phase
- Long term treatment; use lithium or sodium valproate
- Consider psychological intervention (CBT)
What are the NICE recommendations for treating the depression phase in bipolar disorder?
Different treatment tree in bipolar:
> Quetiapine alone (anti-psychotic w/efficacy in bipolar)
» SSRI (Fluoxetine) combined w/olanzapine
»> Olanzapine alone
»» Lamotrigine alone (anti-epileptic)
Which part of the brain is markedly affected in depression? How so?
- The Limbic system ‘emotional brain’
- Reduction in size of the limbic system in patients suffering from severe depression (imaging studies)
The Limbic system consists of:
> Thalamus
> Hippocampus
> Amygdala
What are the different NTs involved in depression?
- 5-HT
- NA
- DA
What is 5-HT responsible for, and how is it affected in depression?
- Anxiety, obsessions, compulsions
- Depression due to decreased levels of 5-HT/serotonin
What is NA responsible for, and how is this affected in depression?
- Alertness, anxiety, interest in life
- Role in rewards and stress (thus decreased levels of NA = depression)
What is DA responsible for, and how is it affected in depression?
- Attention, motivation, reward
- Decreased levels of tyrosine (precursor to DA) results in decreased DA = depression
What are some animal models used for depression, and what do they entail?
Forced swimming test:
- Animal is submerged in narrow cylinder, rat tries to stay afloat (mobile), eventually ‘gives-up’ (non-mobile)
»> If given antidepressant, rat tries to become mobile again
Tail suspension test:
- Similar to above (mobile vs. immobile)
- Learned helplessness
- Stress models (e.g. food deprivation)
- Olfactory bulbectomy; results in loss of interest, but drug restores interest.
What are the aims of managing/treating severe depression? (NICE)
- Manage suicide risk
- Improve QoL
- Prevent relapse
What non-pharmacological options are there for treating severe depression? (NICE)
- High intensity CBT
- Good sleep hygiene
What is considered when deciding on pharmacological therapy for severe depression? (NICE)
- Choice of drug based on Mrs D’s preference
- Adverse effect profile
- Toxicity in overdose
- Interaction w/other treatments
What is first-line pharmacological therapy for treating severe depression? Why are they preferred? Give examples.
Generic SSRIs:
- Citalopram, Fluoxetine, Sertraline, Paroxetine
- Favourable S/E profile; less sedating, fever cardiotoxic effects
- Less toxic in overdose
- Complements CBT
How should a patient be counselled re. medication for severe depression?
- Symptoms worsen before improving (compliance; “bear with them”)
- Takes 2-4 weeks for symptoms to improve
- Vigilant on suicidal ideas, especially when commencing or changing medication
»> Review every 1-2 weeks initially, then every 4 - Take medication for a minimum of 6 months after recover, then titrate down(prevent relapse and minimise side effects)
What are the side effects associated w/SSRIs?
- Nausea & vomiting (common)
- Diarrhoea (and other GI disturbances)
- Dizziness
How is depression treated in U18s?
- Antidepressants avoided; but Fluoxetine is recommended if needed
- Lifestyle advice, including positive coping strategies
»> Evidence is limited
How do SSRIs work?
- Drug binds to 5-HT reuptake transporter on presynaptic membrane
- Thus 5-HT not taken back up from cleft; good level in cleft, 5-HT readily binds to receptors on postsynaptic membrane
= Cellular response
Why do SSRIs take 2-4 weeks to work?
- As some 5-HT binds to 5-HT1 autoreceptor in the pre-synaptic membrane after SSRI binding (to 5-HT reuptake transporter)
- Results in no new 5-HT release from pre-synaptic membrane; there is no exocytosis whilst bound to 5-HT1 autoreceptor
- Meanwhile, MAO and COMT continue metabolising 5-HT to metabolites; 5-HT levels are acutely depleted in clef (hence symptoms worsen before improving)
»> BUT, 2-4 weeks later, 5-HT1 autoreceptor is DOWNREGULATED (desensitised), thus new 5-HT1 can be exocytosed.
What other pharmacological therapies are availible for depression other than first-line SSRIs?
- SNRA; Serotonin-noradrenaline reuptake inhibitor
- TCA; Tricyclic antidepressants
- MAOI; Monoamine oxidase inhibitor
- NaSSA; Noradrenergic and Specific Serotonergic Antidepressant
- NARI; Noradrenaline Reuptake Inhibitor
> > > Antidepressants all similarly effective; patient-dependent decision.
What are SNRIs? Give examples.
Serotonin-noradrenaline reuptake inhibitor (SNRI)
> E.g. Venlafaxine, duloxetine
> Similar to SSRIs
What are TCAs, and where is their place in antidepressant therapy? Give examples.
Tricyclic Antidepressants (TCAs)
E.g. Amitriptyline, imipramine (old school)
- Inhibit 5-HT and NA reuptake
- Sedative properties; H1 receptor antagonism (useful for insomnia)
- Anticholinergic side effects; dry mouth, blurred vision etc. (antimuscarinic)
- Cardiovascular and epileptogenic effects; fatal in overdose
- Lofepramine associated w/lowest risk in overdose
»> S/E profile not as favourable.
What are MAOIs? What is the ‘cheese reaction’? Give examples.
Monoamine oxidase inhibitors (MAOIs)
E.g. phenelzine, tranylcypromine (not used any more)
- Cheese reaction; tyramine (found in cheese, marmite, soya) competes w/NA for reuptake, leading to hypertensive crisis
»> Loads of NA left in cleft; binds to random alpha-adrenoceptors = massive hypertension
What are NaSSAs, and where is their place in treating depression?
Noradrenergic and Specific Serotonergic Antidepressant
E.g. mirtazapine
- α2 auto-heteroreceptor antagonism (normally inhibits NA release); thus permitting 5-HT1 and NA release.
»> Second line after SSRIs, of clinical benefit.
What are NARIs? Give an example.
Noradrenaline Reuptake Inhibitor
E.g. Reboxetine (more NA in cleft)
What is St. John’s Wort, and why should it be avoided?
- Herbal derived from Hypericum perforatum
- Insufficient evidence on its benefit in promoting remission; only slightly more efficacious than placebo
- AVOID in depression; lack of understanding WRT dose, drug interaction and potency
»> Some SSRI-esque activity, increasing 5-HT levels; overdose w/drug therapy at same time?
What is the approach to treating insomnia (w/depression)?
Don’ts:
- Daytime naps
- Caffeine
- Heavy meal at night
- Gadgets before sleep (avoid for hour prior to sleep)
- Alcohol
Do:
- Sleep mask
- Exercise
What approaches can complement sleep hygiene?
- CBT
- Sleeping tablets (e.g. Nytol)
- Benzodiazepines:
> Hypnotics (temazepam, nitrazepam; short half-life) - restrict use to 2-4 weeks. In some cases, taken 2/3 nights per week, rather than daily. - Z-meds; zolpidem, zopiclone, zaleplon (same as BDZs)
- TCAs; H1-receptors, have sedative element
- Melatonin (Circadin); licensed for short-term use in adults > 55 years
