Depression notes, meds, and examples PDF

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Depression Notes

3.20.2020

Epidemiology - 17% of US populations reports a major depressive episode in their lifetime - Depression occurs in women > men, about 2:1 - Average age of onset: mid-20’s o 50% of patients have first episode by age 40 years - Duration: 6 months – 2 years if left untreated o Episodes continue in up to 80% of untreated patients - No correlations between any particular ethnicity, socioeconomic class or lifestyle and depression - Primary action is to shorten depression episode and prevent additional episodes from occurring Depression is Serious - Most common diagnosis is associated with psychiatric hospitalization - Lifetime suicide risk: o 2% MDD treated as outpatient o 4% MDD treated as inpatient o 8% MDD with suicidal ideation/attempt treated as IP - Depression associated with increased mortality rates in individuals 50+ years old - Depression correlated to worse outcomes in chronic medical conditions such as diabetes mellitus due to probable lack of motivation - Biggest risk is suicide Leading Causes of disability - Unipolar depression is the leading cause of disability - Inability to function within a job environment - Costs a lot of money in treatment and loss of money by not working Economic Burden - Estimated to be $30-60 billion - Can result from o Lost workdays o Decreased productivity o Increased healthcare system utilization What does depression look like? - Depressed mood and/or anhedonia are hallmark symptoms - Some patients present as sad, guilt-ridden, and hopeless o Hopelessness: sees no positivity in things; glimmer of light at the end of the tunnel

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Other patients will appear nervous irritable, or agitated Some will complain of somatic problems o Headaches, stomach problems that manifest Psychosis can accompany depression To be diagnosed: sustained depression and/or anhedonia Symptoms must persist for at least 2 weeks

Questions to ask in relation to depression: SIG E CAPS Sleep – more or less Interest – anhedonia Guilt Energy Concentration Appetite Psychomotor agitation – “anxious/ramped up” Suicide Causes of depression Depression associated with medical conditions - Hypothyroidism - Stroke, heart attack - Hepatitis C - Hyperthyroidism: results in more depressive disorders than metabolic or hormonal problems Depression associated with drugs - Alpha-interferon - Resperine - Substance abuse – MDMA, cocaine Pathophysiology of Depression - Etiology not fully understood - Most likely related to a combination of 3 factors

o Genetic predisposition o Environmental influences o Biologic factors  Biogenic amines (NE, 5HT, DA)  Non-monoamine compounds (CRF) Biogenic Amine Theory - Implies having an imbalance of too little of one or more of the monoamines Neurotransmitter - A chemical substance released from a neuron that transmits a nerve impulse across a synapse - 3 primary neurotransmitters thought to be involved in depression (the monoamines) o Serotonin o Norepinephrine o Dopamine Monoamine reuptake transporters - Responsible for removing neurotransmitters from the synapse - Inhibition of these transporters  increases level of neurotransmitter in the synapse - Specific transporters for 5HT, NE, DA Monoamine oxidase - Metabolizes (destroys) monoamines  decreases neurotransmitter levels - Inhibition of this enzyme  increases neurotransmitter levels

Treatment Approaches - Pharmacotherapy o Available, less expensive

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Psychotherapy (not as much availability, can be expensive, requires more time) o Cognitive behavioral therapy o Interpersonal therapy Electroconvulsive therapy (ECT) Combination of both drug and therapy has the best results

*Antidepressants can be used for neuropathic pain and other usages such as anxiety* Potential Drug Targets - Serotonin transporter - Norepinephrine transporter - Dopamine transporter - NE receptors (unknown how they work) - 5HT receptors (unknown how they work) - Monoamine oxidase Selective Serotonin Reuptake Inhibitors (SSRIs) - Most commonly used antidepressants in the world o Drug choice primarily picked for side effects. Relatively safe. - Just targets serotonin - Medications: Fluoxetine, Sertraline, Paroxetine, Citalopram, Escitalopram, Fluvoxamine - MOA: inhibit serotonin transporter - Generally dosed once a day - Typically given in the morning, but can be taken any time of the day (convenient) - No data conclusively demonstrates that any one SSRI is more effective than any other on a population basis - ADRs: o Side effects related to increased serotonergic stimulation as well as nonselective receptor profiles of some agents o Sedation, nausea, sleep disturbances (insomnia), sexual side effects (bothers people the most), weight gain Serotonin and Norepinephrine Reuptake Inhibitors (SNRIs) - Inhibit neuronal reuptake of serotonin and norepinephrine Venlafaxine - Serotonin reuptake inhibition across dosage range o At low doses it blocks serotonin. Essentially acts like an SSRI. - Norepinephrine inhibition at doses >200mg/day o Dose related increases in blood pressure - Adverse events o Nausea, GI complaints, insomnia, sexual side effects  serotonin ADRs o Increased BP, sweating, agitation  norepinephrine ADRs - Pro drug!

Desvenlafaxine - Active metabolite of venlafaxine (active form!) - Adverse events o Similar to venlafaxine o GI, nausea, BP, sexual dysfunction, etc. Duloxetine - Balanced norepinephrine and serotonin reuptake inhibition across dosage range - FDA approved for neuropathic pain associated with diabetes mellitus o You’ll see it more used for neuropathic pain than for depression - ADRs: o Similar to venlafaxine o Significant rates of nausea Atypical Antidepressants Bupropion - MOA: inhibition of dopamine and norepinephrine reuptake - FDA approved for smoking cessation - ADRs: o Lowers seizure threshold  Contraindicated for patients with history of seizures  Takes less stimulation for someone to experience a seizure o Lower incidence of sexual side effects - No serotonergic effects Mirtazapine - MOA: enhances norepinephrine and serotonin activity - ADRs: o Sedating antihistaminic effect  Taken at bedtime  Useful for insomnia  More common at lower doses  Increased NE activity at higher doses  Significant weight gain  Low rate of sexual dysfunction - Possibly works by increasing sensitivity or as an agonist - Not a first line drug because the sedative effect can have a hangover effect that carries over in another day Trazodone - MOA: enhances serotonin activity - Very sedating – used to treat insomnia o Not used as much for depression as it is a sleeping aid

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