Lesson 20 Antidepressants

Increased Prescriptions: 1990s-2000s: prescriptions for antidepressants doubled from 80 million to 160 million. By 2007, antidepressants became the most prescribed medication.
Clinical Trials: Safety and efficacy are tested during trials, with ongoing post-trial surveillance. Special populations like children and pregnant women often excluded from these studies.
Concerns in Pregnancy: Rising concerns related to antidepressant use during pregnancy; refer to abstract PMID 19480468 for detailed analysis of risks vs. benefits.
Non-recreational Nature: Antidepressants, unlike stimulants, are purely therapeutic and lack euphoria or addiction in their side effects.

Popular Names: Paxil, Zoloft, Prozac, all belong to the category of SSRIs (Selective Serotonin Reuptake Inhibitors).
Mechanism: SSRIs increase serotonin availability in the synapse by inhibiting serotonin recycling.
Evolution of Treatment: Treatments for depression have included lithium and electroshock therapy; depression recognized as a legitimate biochemical illness largely due to efforts from Surgeon General David Satcher during the Clinton administration.

SSRIs: Inhibit recycling of serotonin.
Tricyclic Antidepressants: (e.g., doxepin, imipramine) impact all monoamine recycling.
Monoamine Oxidase Inhibitors (MAOIs): Inhibit the enzyme monoamine oxidase, affecting metabolism of monoamines, discussed further regarding drug selegiline.

Dosage Variability: Effective dosage varies by medication and patient. For Zoloft, typical initial prescriptions are 25-50 mg, max 200 mg; lethal dose estimated at 80 mg/kg.
Drug Administration: Most antidepressants taken orally once a day, with selegiline being an exception requiring careful dietary management. Transdermal patches developed to avoid dietary interactions.

Metabolism: Antidepressants metabolized by enzymes CYP2D6, CYP2C9, CYP2C19.
**Binding Sites: **
- SSRIs: Bind to serotonin recycling transporter (SERT).
- Tricyclics: Bind to various monoamine transporters.
- MAOIs: Bind to monoamine oxidases.
Impact of Binding: Inhibition increases monoamine availability; however, binding dynamics can vary significantly among different antidepressants.

Non-addictive Nature: SSRIs, MAOIs, tricyclics are not considered addictive despite enhancing dopamine availability. A dependency may arise (feeling depressed after cessation), but not classified as addiction, which typically involves harmful substance use.
Atypical Antidepressants: Some may have addictive potential; prescribed less frequently with stricter guidelines.

Meta-analyses on Efficacy: Recent studies show mixed results; critical to evaluate what metrics and individual biochemical factors affect effectiveness.
Potential Side Effects:
- Risk of suicide – monitoring essential due to paradoxical mood elevation.
- Individual variations in efficacy based on personal biochemistry and interactions with other medications.

Anticholinergic effects: Reduced parasympathetic function.
Sedation: Increased sleepiness.
Orthostatic Effects: Dizziness upon standing.
Sexual Effects: Changes in libido.
GI Upset: Reduced digestive function.
Cardiac Arrhythmias: Risk monitored in pregnant clients.
Agitation/Insomnia: Increased wakefulness due to excitatory neurotransmitter increases.
Weight Gain: Possible correlation with improved mood and increased appetite.

Emergency Hotline: Suicide & Crisis Hotline: 988
Comparative Analysis: Further evaluation of paroxetine (SSRI) and imipramine (tricyclic) for understanding efficacy and acceptability.