Psychiatry

• Antidepressants


  Drugs used to treat depression and other mood disorders
• Mood Stabilizers


  Drugs used to treat bipolar disorder and other mood disorders
• ECT (Electroconvulsive Therapy)


  A physical treatment involving the induction of a modified seizure triggered with controlled electric current
• General Pharmacology Strategies


  1. Indication: Establish a diagnosis

  2. Identify the target symptoms that will be used to monitor therapy response

  3. Choice of agent and dosage: Select an agent with an acceptable side effect profile

  4. Use the lowest effective dose

  5. Remember the delayed response for many psych meds and drug-drug interactions
• Indications for Antidepressants


  • Unipolar and bipolar depression
  • Organic mood disorders
  • Schizoaffective disorder
  • Anxiety disorders including OCD, Panic, Social Phobia
  • PTSD
  • Premenstrual dysphoric disorder
  • Impulsivity associated with personality disorders
  • Neuropathic Pain
• General guidelines for Antidepressant use

  • Antidepressant efficacy is similar so selection is based on past history of a response, side effect profile and coexisting medical conditions
  • There is a delay typically of 2-4 weeks after a therapeutic dose is achieved before symptoms improve
  • If no improvement after a trial of adequate length (at least 2 months) and adequate dose, either switch to another antidepressant or augment with another agent
• Classification of Antidepressants


  • Tricyclics (TCAs)
  • Monoamine Oxidase Inhibitors (MAOIs)
  • Selective Serotonin Reuptake Inhibitors (SSRIs)
  • Serotonin/Norepinephrine Reuptake Inhibitors (SNRIs)
  • Novel Antidepressants
• Tertiary TCA's


  Have tertiary amine side chains, act predominantly on serotonin receptors, prone to cross react with other types of receptors which leads to more side effects
• Tertiary TCA's


  • All TCA are very effective but unacceptable side effect profiles
• Examples of Tertiary TCA's


  • Imipramine
  • Amitriptyline
  • clomipramine
• Side effects of TCAs

  • Antihistaminic: sedation and weight gain
  • Anticholinergic: dry mouth, dry eyes, constipation, memory deficits and potentially delirium
  • Antiadrenergic: orthostatic hypotension, sedation, sexual dysfunction
  • Lethal in overdose (even a one week supply can be lethal)- agitation, delirium, BP dysregulation, respiratory depression, coma
  • Can cause QT lengthening even at a therapeutic serum level, also flattened T waves, depressed ST segments
  • Discontinue before surgery - can lead to hypertensive crises
• Secondary TCA's


  Are often metabolites of tertiary amines, primarily block norepinephrine, side effects are the same as tertiary TCAs but generally are less severe
• Examples of Secondary TCA's

  • Desipramine
  • Notriptyline
• Monoamine Oxidase Inhibitors (MAOIs)


  Bind irreversibly to monoamine oxidase preventing inactivation of biogenic amines leading to increased synaptic levels
• Side effects of MAOIs

  • Orthostatic hypotension, weight gain, dry mouth, sedation, sexual dysfunction and sleep disturbance
  • Hypertensive crisis can develop when MAOI's are taken with tyramine-rich foods or sympathomimetics
• Serotonin Syndrome with MAOIs

  Abdominal pain, diarrhoea, sweats, tachycardia, HTN, myoclonus, irritability, delirium, hyperpyrexia, cardiovascular shock and death
• Selective Serotonin Reuptake Inhibitors (SSRIs)


  Block the presynaptic serotonin reuptake, treat both anxiety and depressive symptoms, very little risk of cardiotoxicity in overdose
• Common side effects of SSRIs

  • GI upset, sexual dysfunction (30%), anxiety, restlessness, nervousness, insomnia, fatigue or sedation, dizziness
  • Can develop a discontinuation syndrome with agitation, nausea, disequilibrium and dysphoria
• Paroxetine (SSRI)


  Pros: Short half life with no active metabolite, sedating properties offer good initial relief from anxiety and insomnia

  Cons: Significant CYP2D6 inhibition, sedating, weight gain, more anticholinergic effects, most likely to cause a discontinuation syndrome
• Sertraline (SSRI)


  Pros: Very weak P450 interactions, short half life with lower build-up of metabolites, less sedating

  Cons: Max absorption requires a full stomach, increased number of GI adverse drug reactions
• Fluoxetine (SSRI)


  Pros: Long half-life so decreased incidence of discontinuation syndromes, initially activating so may provide increased energy

  Cons: Long half life and active metabolite may build up, significant P450 interactions, initial activation may increase anxiety and insomnia, more likely to induce mania
• Citalopram (SSRI)


  Pros: Low overall inhibition of P450 enzymes so fewest drug-drug interactions, intermediate half life leads to low incidence of discontinuation syndrome

  Cons: Can be sedating, GI side effects
• Selective Serotonin/Norepinephrine reuptake inhibitors (SNRIs)


  Inhibit both serotonin and noradrenergic reuptake like the TCAS but without the antihistamine, antiadrenergic or anticholinergic side effects, used for depression, anxiety and possibly neuropathic pain
• Venlafaxine (SNRI)


  Pros: Minimal drug interactions and almost no P450 activity, short half life and fast renal clearance avoids build-up

  Cons: Can cause a 10-15 mmHG dose dependent increase in diastolic BP, may cause significant nausea, can cause a bad discontinuation syndrome, noted to cause QT prolongation, sexual side effects in >30%
• Mirtazapine (Novel Antidepressant)


  Pros: Different mechanism of action may provide a good augmentation strategy to SSRIs, can be utilized as a hypnotic at lower doses secondary to antihistaminic effects

  Cons: Increases serum cholesterol and triglycerides, very sedating at lower doses, associated with weight gain
• Classes of Mood Stabilizers

  • Lithium
  • Anticonvulsants
• Indications for Mood Stabilizers

  • Bipolar Disorder
  • Schizoaffective disorder
  • Cyclothymia
  • Impulse control disorders
  • Intermittent explosive disorders
  • Recurrent depressive disorder
• Lithium


  Only medication shown to reduce suicide rate in bipolar disorder, effective in long-term prophylaxis of both mania and depressive episodes in 70% of patients
• Factors predicting positive response to lithium

  • Prior long-term response or family member with good response
  • Classic pure mania
  • Mania is followed by depression
• Lithium contraindications


  • Cardiac failure
  • Renal disease
  • Thyroid disease
  • Pregnancy
• Lithium monitoring


  Before starting: Get baseline Creatinine, TSH, ECG FBC, pregnancy test in women

  Steady state achieved after 5 days- check 12 hours after last dose, once stable check every 3 months and TSH and Creatinine every 6 months

  Goal blood levels between 0.6-1.2 mcg/ml
• Lithium side effects


  • GI distress including reduced appetite, nausea/vomiting, diarrhoea
  • Thyroid abnormalities
  • Nonsignificant leukocytosis
  • Polyuria/polydypsia secondary to ADH antagonism, can cause interstitial renal fibrosis
  • Hair loss, acne
  • Reduces seizure threshold, cognitive slowing, intention tremor
• Lithium toxicity


  • Mild- levels (1.5-2.0) vomiting, diarrhea, ataxia, dizziness, slurred speech, nystagmus

  Moderate-(2.0-2.5) nausea, vomiting, anorexia, blurred vision, clonic limb movements, convulsions, delirium, syncope

  Severe- >2.5 generalized convulsions, oliguria and renal failure
• Sodium Valproate


  As effective as Lithium in mania prophylaxis but not as effective in depression prophylaxis, acts through GABA receptors
• Factors predicting a positive response to Sodium Valproate

  • Rapid cycling patients (females>males)
  • Comorbid substance issues
  • Mixed disorders
  • Comorbid anxiety disorders
• Sodium Valproate monitoring


  Before med is started: baseline liver function tests (LFT), pregnancy test and FBC, start folic acid supplement in women

  Steady state achieved after 4-5 days -check 12 hours after last dose and repeat FBC and LFT

  Goal target levels is between 50-125 mcg/ml
• Sodium Valproate side effects

  • Thrombocytopenia and platelet dysfunction
  • Nausea, vomiting, weight gain
  • Elevated liver enzymes
  • Sedation, tremor
  • Increased risk of neural tube defect 1-2% vs 0.14-0.2% in general population secondary to reduction in folic acid
  • Hair loss
• Carbamazepine


  First line agent for acute mania and mania prophylaxis, inactivates sodium channels
• Factors predicting a positive response to Carbamazepine

  • Rapid cyclers

  Mixed patients
• Carbamazepine monitoring


  Before med is started: baseline liver function tests, FBC

  Steady state achieved after 5 days -check 12 hours after last dose and repeat tests

  Goal target levels 4-12mcg/ml, need to check level and adjust dosing after around a month because it induces its own metabolism