affective disorders

Nota:

• anxiety is one of many forms of depression

1. Generalised Anxiety Disorder (GAD)
   1. Benzodiazepines

      Nota:

      • Short term use only. Addictive!! withdrawal symptoms: -anxiety -insomnia -autonomic hyperactivity -seizures
      1. lorazepam, citalopram, chlordiazepoxide
   2. 5HT1A agonists

      Nota:

      • doesn't work? anxiolytic effect by reduced 5-HT transmission
      1. Buspirone
   3. SSRIs
      1. fluoxetine, citalopram, sertaline
   4. SNRIs
      1. venlaflaxine, duloxetine
   5. tricyclic antidepressants
      1. clomipramine
   6. psychological therapies
      1. Cognitive Behavoiural Therapy
2. Panic disorder
   1. SSRIs
   2. benzodiazepines
   3. behavioural therapy
   4. CBT
3. Phobias
   1. avoidance
4. Obsessive Compulsive Disorder (OCD)
   1. behavioural therapy
   2. CBT - less useful
   3. pharmacotherapy - less effective
      1. SSRIs
      2. antipsychotics
      3. clonazepam

1. SSRIs
2. tri-cyclic antidepressants
3. Serotonin and Noradrenaline Reuptake Inhibitor (SNRI)
   1. venlafaxine
4. Mirtazapine

   Nota:

   • presynaptic alpha2 adrenoreceptor antagonist
5. Monoamine Oxidase Inhibitors
   1. phenelzine, tranylcypromine

1. acute mania
   1. antipsychotics

      Nota:

      • MOA in mania not clear "retune dysfunctional circuits" -antagonise dopamine D2 receptor (reduce psychotic symptoms) -antagonise serotonin 5HT2A receptors (reduction of non-psychotic symptoms, possibly as a result of inhibition of glutamate hyperactivity)
   2. valporate

      Nota:

      • MOA uncertain possible MOA 1. inhibition of voltage sensitive Na channels - reduced Na influx and subsequent glutamate excitatory neurotransmission 2. Boosting actions of GABA by: -inhibition of GABA reuptake -enhancing GABA release -inhibiting GABA metabolism by GABA transaminase 3. regulation of downstream signal transduction cascades (neuroprotection and long term plasticity)
   3. lithium

      Nota:

      • MOA unclear (however used in bipolar disorder >50 years) promotes neuroprotection and long term plasticity of dysfunctional neuronal circuits by?: -inhibition of second messenger enzymes. impact on signal transduction beyond neurotransmitter receptor - modulation of key proteins(affecting signal transduction) -inhibition of signal transduction cascades
      • effective in acute mania, acute depression, and long term prophylaxis TOXIC medicine (narrow therapeutic index) blood monitoring required t1/2 = 24hrs dose titrated according to blood levels once stable therapeutic range reached blood tests monthly for 3mths then 3 monthly 6 monthly thyroid tests recommended NSAIDs & ACE inhibitors increase Li levels by reducing renal clearance
   4. severe short term behavioural symptoms
      1. benzodiazepines
   5. carbamazepine
2. prophylaxis of mania

   Nota:

   • long term treatment of manic episode is considered when: -manic episode associated with significant risk and adverse consequences -patient with bipolar I (mania predominates) has had two or more acute episodes
   • -recommended treatment continues for at least 2 years -may continue for up to 5 years if: *history of frequent episodes *severe psychosis *comorbid substance abuse *on-going stressful life events *poor social support
   1. lithium
   2. valporate
   3. olanzapine
   4. carbamazepina
3. prophylaxis of depression

   Nota:

   • risk of antidepressant drugs 'switching' to mania
   1. lithium
   2. lamotrigine
      1. not licensed in UK to treat bipolar
   3. antipsychotics