Antidepressant Drugs

Antidepressant Drugs

1. Types of Antidepressants

   • Tricyclics
     • operate by blocking transporter proteins that reabsorb serotonin, dopamine & norepinephrine into presynaptic neurone after release
       • results in prolong the presence of NT in synaptic cleft, continue stimulating postsynaptic cell
     • Also block histamine receptors, acetycholine receptors & certain sodium channels
       • blocking histamine causes drowsiness
       • blocking acetycholine leads to dry mouth and hard to urinate
       • block sodium channels causes heart irregularities
   • Selective Serotonin Reuptake Inhibitors (SSRIs)
     • specific to NT serotonin
     • prozac blocks reuptake of serotonine
     • produce milder side effects than try but effectiveness is about the same
     • Serotonin Norepinephrine Reuptake Inhibitors (SNRIs)
       • block the reuptake of serotonin and norepinephrine
   • Monoamine Oxidase Inhibitors (MAOIs)
     • block enzyme monoaime oxidase (MASO
       • presynaptic terminal enzyme that metabolises catecholamines and serotonin into active forms.
         • when block this enzyme the presynaptic terminal has more of its transmitter available for release
     • last resort after try and SSRI
     • must avoid foods containing syramine (cheese etcs
       • combo of tyramine and MAOIs increases blood pressure
   • atypical antidepressant
     • buropion inhibits reuptake of dopamine and to some extent norepinephrine but not serotonin
   • St Johns Wort
     • advantage of being less expensive than anti depressants
     • advantage/disadvantage available without a prescription
       • can end up taking inappropriate amounts which is dangerous
     • all mammals have liver enzyme breaks down plant toxin
       • increases effectiveness of that enzyme
         • this also breaks down medicines and makes them ineffective

2. How do Antidepressants work

   • increase presence of serotonin or other NT at sun apse so problem is too little of the NT
     • blood metabolites, people with sep have approx normal levels of release of NT
       • some studies show people with dep have increase in serotonin release
         • BARTON ET AL 2008
         • possible to decrease serotonin levels suddenly by consuming all amino acids except tryptophan, procurer to serotonin
           • decrease in serotonin doesn't provoke any feelings of dep
             • NEUMEISTER ET AL 2004
   • would expect drugs to have diff effects but most have equal effects on NT
     • two studies, patients failed respond to antidep drug
       • one added second drug and other switched
         • patients who didn't respond to first, responded to second
           • RUSH ET AL 2006
       • neither did control group so no conclusions found
   • time course is threat in term of NT
     • antidep produce effects on NT in synapses within min-hrs depending on drug
       • takes 2 weeks for it to start working
         • delay of benefits suggests increase level of NT at synapses doesn't explain the benefits of drugs
   • focus on neurotophins
     • neurotophins aid in survival, growth and connections of neurons
     • most with deo have lower levels of neurotrophin called brain-derived neutotrophic factor BDNF
       • important for synaptic, plasticity,learning and proliferation of new neurones in hippo
       • low BDNF people with dep have smaller hippo, impaired learning, reduced production of new hippo neurons
     • prolonged use of antidep increases BDNF prod and improves learning and formation of new neurons
       • takes weeks
         • time course for BDNF and changes in hippo matches time course for behavioural recovery
           • procedures block neuron production also block behavioural benefits of antidep drugs
     • BDNF alone doesn't auto elevate mood but helps by facilitating new learning that builds new synapses and removes old ones
       • mode of action explains why antidep help people in dep but fail to elevate mood for normal people