Anxiety and Depression
Depression:
 Definition: (DSM-5)
o > 5 of the following in the same 2 week period
 Depressed mood nearly every day
 Diminished pleasure in most/all activities on most days
 Significant weight loss or gain OR increased or decreased appetite
 Insomnia or hypersomnia nearly every day
 Psychomotor agitation or retardation on most days
 Fatigue or loss of energy on most days
 Feeling worthless or inappropriate guilt most days
 Decreased concentration or indecisiveness most days
 Recurrent thoughts of death
 Symptoms: SIGECAPS
o Decreased sleep
o Decreased interest
o Increased guilt
o Decreased energy
o Decreased concentration
o Increased or decreased appetite
o Decreased psychomotor
o Increased suicide
Pathophysiology:
 Four proposed mechanisms
o Biogenic amine hypothesis  depression linked to a deficiency of catecholamines (NE,
serotonin, dopamine)
o Desensitization hypothesis  acute increased in neurotransmitters may cause adaptive changes
in receptor sensitivity
o Dysregulation hypothesis  possible impairment of neurotransmitter systems in one or more
regulatory or homeostatic brain mechanisms
o Dopaminergic hypothesis  decreased dopaminergic neurotransmission may play a role in
depressive symptoms
Antidepressants: all carry a BBW for increased risk of suicide
 1st line  SSRIs, SNRIs, Bupropion, Mirtazepine
 SSRIs  Fluoxetine, Sertraline, Paroxetine, Citalopram, Escitalopram, Fluvoxamine
o MOA  inhibit the reuptake of serotonin from the synaptic cleft
o AE  GI upset, CNS effects, sexual dysfunction, serotonin syndrome, hyponatremia
o Contraindicated with Linezolid, IV methylene blue, and MAOIs (current or within 2 weeks)
 SNRIs  Duloxetine, Venlafaxine, Desvenlafaxine, Milnacipran, Levomilnacipran
o MAOIs  inhibits reuptake of serotonin and norepinephrine from the synaptic cleft
o AE  GI upset, CNS effects, sexual dysfunction, serotonin syndrome, SIADH
o Contraindicated with Linezolid, IV methylene blue, and MAOIs (current or within 2 weeks)
 Mixed Serotonin Modulators  Vortioxetine (Trintellix), Vilazodone (Viibryd)
 Norepinephrine Dopamine Reuptake Inhibitor (DNRI)  Bupropion
o MOA  inhibits reuptake of NE and dopamine
o AE  anxiety, insomnia, headache, nausea, tremor, weight loss, dry mouth, seizures (dosedependent)
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o Contraindicated with Linezolid, IV methylene blue, and MAOIs (current or within 2 weeks),
seizure history, eating disorders, abrupt alcohol or sedative
Tetracyclic  Mirtazapine
o Inhibits alpha-2 receptors on pre-synaptic neuron to increase release of serotonin and NE
o SE  sedation, increased appetite, weight gain, dizziness, HLD/HTGD
o Contraindicated with Linezolid, IV methylene blue, and MAOIs (current or within 2 weeks)
TCAs  Amitriptyline, Nortriptyline, Imipramine, Desipramine, Doxepin, Amoxapine, Clomipramine
o Block serotonin and NE reuptake
o AE  they have TONS; that is why they are not first line agents
o Contraindications  acute/recent MI, history of prolonged QTc, narrow angle glaucoma,
tachycardia, Linezolid, IV methylene blue
o Think TCAs  Tremor, CV effects, Anticholinergic effects, Sedation/Seizures
MAOIs  Isocarboxazid, Phenelzine, Selegiline, Moclobemide
o MOA  irreversibly inhibit monoamine oxidase; increases NE, serotonin, and dopamine within
neuronal synapse
o AE  way too many to type.
o Contraindications  cerebrovascular disease, hepatic impairment, uncontrolled HTN, Linezolid,
IV methylene blue
Side effects of antidepressants:
o Suicidal thoughts
 Seen in teens and young adults
 Increase in energy without resolution of depression
 Greatest risk in first few weeks
o Sexual dysfunction  common with all BUT Bupropion
o HA/N/V
 Caused by the increase in serotonin
 Should resolve as depression resolves
Serotonin Syndrome:
 Signs and symptoms:
o Tachycardia, HTN
o Mydriasis
o Hyperreflexia, clonus, tremor
o Diaphoresis, vomiting, diarrhea
o Agitation, altered mental status
 Management:
o DC offending agent
o Supportive care
o Benzodiazepine for agitation
Duration of Treatment:
 1st episode  6-12 months
 2nd episode  3 years once remission is reached
 > 3 episodes  indefinite treatment
Increase Suicide Monitoring in:
 Treatment initiation
 Dose increases
 Younger patients
Barriers to ALL Behavioral Health Treatment:
 Stigma, cost, and disjointed health care delivery systems
Diagnosis of Both:
 Medical diagnosis consists of objective information and presenting symptoms
 Behavioral diagnosis is mostly subjective and relies on symptoms and assessment measures from patient
and family
 Lots of diagnosis or risk assessment comes from questionnaires in the outpatient setting
o PHQ-2
o PHQ-9
o HAM-D
o BDI
o GDS
o QIDS
o WHO-5 Well Being Index
 All diagnoses will refer back to the DSM-5 Criteria (addressed earlier)
Anxiety:
 Persistent, excessive, uncontrollable and unrealistic worry about everyday things
Diagnostic Criteria:
 Excessive anxiety/worry lasting for > 6 months that is difficult to control
 Presence of > 3 symptoms for > 1 month:
o Restlessness, feeling keyed up, or on edge
o Easily fatigues
o Difficulty concentrating or mind going blank
o Irritability
o Muscle tension
o Sleep disturbances
 Significant distress of functional impairment
Risk Factors:
 Women > men
 Stress
 Medications
 Medical conditions
Non-Pharmacological Interventions:
 Exercise
 Psychotherapy
 Relaxation/Meditation therapy
Pharmacotherapy Options:
 SSRI or SNRI  first line
 Benzodiazepine or Atypical  Buspirone  second line
 Antihistamine  Hydroxyzine
 Other  Antipsychotics, Pregabalin  adjunctive
Benzodiazepines:
 MOA  increase GABA receptor activity
 AE  CNS depression, DC syndrome
 Contraindicated  SA history, respiratory disorders, pregnancy/lactation/labor, significant hepatic
disease
 Good for acute management, adjunctive with initiation of antidepressant
 May contribute to depressive symptoms
 In geriatric patients, prefer LOT (Lorazepam, Oxazepam, Temazepam)
Buspirone:
 MOA  partial serotonin agonist
 Efficacious but inferior to benzo
 Non-addictive and well-tolerated
 No immediate anxiolytic effect
Hydroxyzine:
 MOA  histamine and serotonin receptor antagonist
 Anticholinergic and antihistaminic side effects
 Active metabolite is cetirizine
 Onset of action is within 30 minutes
Pregabalin:
 MOA  binds voltage-gated calcium channels
 Good for acute management with anxiolytic effects similar to benzos
 Potential alternative to long-term benzo
 Potential for abuse/dependence
Second Generation Antipsychotics:
 MOA  partial serotonin agonist
 Augmentation therapy for refractory disease, psychosis, or severe agitation
 Olanzapine, Risperidone, and Quetiapine have the most evidence for support