Depressive, Anxiety and Attention Disorders and Treatment Flashcards
What complex neuropsychiatric disorders that we know as mood disorders mess with emotion? Cognition? Visceral activity? Psychomotor activity?
- emotion - mania, depression
- Cognition - thought disorder, memory, concentration, focus, executive function
- Visceral activity - appetite, bowel function, nausea
- Psychomotor activity - sleep, insomnia, agitation, psychomotor retardation
Are mood disorders genetic?
- They can be inherited, so yes
- Bipolar disorder tends to be the more heritable of them all
- However, no clear etiology has emerged for any psychiatric illness
Are depression and bipolar disorder best thought of as chemical imbalances?
- No, the long-standing chronic disease state is better described as a full disruption in neural circuitry
- Involves the amygdala, prefrontal cortex, cingulated, striatum, thalamus, hippocampus
- Serotonin, NE and DA play an important role in modulating these circuits
Describe how depression is often associated with neuroendocrine dysfunction.
• Activation of HPA axis to stress is well-known
• Neurons in paraventricular nucleus of the hypothalamus secrete corticotropin-releasing factor (DRF)
• Stimulates the synthesis and release of ACTH (adrenocorticotropin) from the anterior pituitary
• ACTH then stimulates synthesis and release of glucocorticoids (cortisol) from the adrenal cortex
• These exert profound effects on general metabolism and affect behavior
• The activity of the HPA is controlled by several brain pathways including the hippocampus and the amygdala
○ Hippocampus is inhibitory, amygdala excitatory
• Sustained elevations of glucocorticoids, like under severe and prolonged stress, may damage hippocampal neurons
• This may involve a reduction of dendritic branching and loss of dendrites and loss of glutamatergic synaptic inputs
• The inhibitory control that the hippocampus exerts on the Hpa axis is thus diminished and that results in a further increase in circulating glucocorticoid levels
○ Hippocampal atrophy may be observed
What are the DSM-V depressive disorders?
- Disruptive mood dysregulation disorder
- MDD (major depressive disorder)
- Depressive disorder due to a medical condition
- Persistent depressive disorder (dysthymia)
- Substance/medication-induced depressive and related disorder
- Premenstrual dysphoric disorder
- Unspecified and other specified depressive disorder
What are the bipolar course and episode specifiers?
- With anxious distress
- With peripartum onset
- With atypical features
- With psychotic features
What are the depression course and episode specifiers?
- With mixed features
- With melancholic features
- With seasonal pattern
- With catatonia
What’s the time course for ddx of depression?
- Must experience 5 or more of the symptoms
- Must persist for 2 weeks or more
- Must experience sad mood or anhedonia
- Must be a change from baseline
What are the symptoms of depression?
- SIGECAPS
- Sleep
- Interest
- G - guilt
- E - energy
- C - concentration
- A - anhedonia
- P - psychomotoric changes
- S - suicidal ideation
What course makes you think atypical depression?
• Mood reactivity
• Leaden paralysis
• Reverse neurovegetative symptoms
○ Increased appetite, weight gain, hypersomnia
What is melancholic depression?
Mood worse in morning, early morning awakening, anorexia, weight loss, guilt, psychomotor retardation
Describe bipolar disorder
• Best considered on a spectrum
• Ranging from extreme mood swings to cyclothymia to hypomanias and major depression
• Can range to frank (real) manias (bipolar I)
• Manias can be induced by medications (antidepressants or steroids are more common) or brain injuries
○ If induced by these events they are called secondary manias
• Bipolar disorder symptoms can be divided into 4 domains
○ Manic mood and behavior
§ Euphoria, grandiosity, pressured speech, impulsivity, excessive libido, recklessness, social intrusiveness, diminished need for sleep
○ Dysphoric mood and behavior
§ Depression, anxiety, irritability, hostility, violence or suicide
○ Psychosis
§ Delusions and halllucinations
○ Cognitive symptoms
§ Racing thoughts, distractability, disorganization, inattentiveness
• No clear etiology. More inherited than other psych conditions
How do you diagnose bipolar disorder?
• Need mania or hypomania. With full mania that bumps the dx to bipolar I
• Mania - particular symptoms and particular rules for course of disease
○ Distinct period of abnormally and persistently elevated, expansive or irritable mood
○ Persistently increased goal-directed activity or energy, present most of the day nearly every day lasting at least 1 week
○ Or any duration if hospitilization is necessary
○ PLUS 3 or more symptoms (euphoric)
○ OR 4 or more symptoms (if irritable)
• Symptoms - DIGFAST
• Distractibility, insomnia, grandiosity, flight of ideas, activity, speech, thoughtlessness
• The symptoms have to co-occur and cause significant problems in daily life
What are the typical medical illnesses that can masquerade as a mental illness?
- Endocrine - cushings, hyper/hypothyroidism, steroids
- Infections - HIV, influenza, meningitis, CJD
- CNS - stroke, tumor, MS, epilepsy
- Metabolic - hypercalcemia
What substances of abuse can manifest as mood disorders either through toxicity or withdrawal?
- Cocaine, alcohol, amphetamine/stimulants
- Hallucinogens (LSD, PCP, mescaline)
- Benzodiazepines
What are the prescribed medications that have side effects that can look like mood disorders?
- Amantadine
- Methyldopa withdrawal
- Interferon
- Steroids
- Chemotherapy agents
What is considered optimal treatment of mood disorders?
- For mood disorders, the optimal treatment is both behavioral AND medication therapy
- Pharm and psychotherapy
- Depression can be only psychotherapy, but bipolar needs meds
What are the three different phases of mood disorder treatment?
- Acute - 0-3 months (50% may stop treatment here)
- Continuation (4-9 months) - 65-75% may stop treatment
- Maintenance (years)
What’s the treatment paradigm for depression?
• Ssri and snri almost immediately block the reuptake of serotonin and NE, antidepressant effects take weeks to work
○ Likely b/c downstream changes that are caused by the blockade of NT
• The exact mechanism of antidepressant efficacy is currenlty unclear
○ May ultimately alter the expression of brain-derived neurotrophic factor (BDNF)
○ This increases neuronal growth (specifically hippocampal volume)
• ALL current FDA-approved pharm treatments target NT systems and boost synaptic actions
○ NE, 5HT, DA
• ALL current treatments have a 4-16 week delay before achieving antidepressant effect
• ECT = electroconvulsive therapy - the only approved treatment for depression that produces more rapid response
• Overall response rate to antidepressants in first 8 weeks is 67%
○ Only about 1/3 will achieve remission with SSRI initial therapy regimen
• All approved meds appear to have the same efficacy
Describe the different types of antidepressants
• Generally broken into 5 broad categories (there is no right antidepressant. Consider individual risks and benefits)
○ SSRIs - selective serotonin reuptake inhibitors
§ Block 5HT pre-synaptic reuptake pump
○ SNRIs - selective norepinephrine reuptake inhibitors
§ Block both NE and 5HT reuptake pumps
○ (TCA’s)- Tricyclic antidepressants
§ Block reuptake of 5HT and NE (also DA but not as much) and also blocks H1, muscarinic cholinergic receptors and alpha1 receptors
○ MAOIs - monoamine oxidase inhibitors
§ Irreversibly inhibit MAO-A and MAO-B, increasing levels of 5HT and NE
○ Other (mixed)
• Mirtazapine
○ Blocks several 5HT receptors AND alpha 2 receptors
• Buproprion
○ Increases whole body NE, weakly blocks reuptake of DA
• Trazodone and nefazodone
○ Most potent action is blockade of post-synaptic 5HT2
○ Block reuptake of 5HT and NE
• Vilazodone (newer guy)
○ SSRI + 5HT1a partial agonist
What are the important SNRIs?
- Venlafaxine (vader)
- Desnvenlafaxine (definately)
- Duloxetine (defines)
- Milnaciprin (mighty)
- levomilnaciprin (levitation)
What are the important SSRIs?
- Fluoxetine (Father)
- Paroxetine (Priest)
- Sertraline (says)
- Citalopram (catholic)
- Escitalopram (escatology)
- Fluvoxamine (following)
- vilazodone (valentine’s day)
What are the important MAOIs?
- Phenelzine (poop)
- Selegeline (transdermal) (stinks)
- Tranylcypromine (taken)
- isocarboxazid (internally)
What are the important “other” antidepressants?
- Mirtazapine
- Buproprion
- Trazodone
- Nefazodone (also an SSRI)
What are the important TCAs?
- Amytriptyline (anybody)
- Nortriptyline (never)
- Desipramine (dancing)
- Imipramine (impractically)
- Doxepin (decides)
- Trimipramine (to)
- Protriptyline (practice)
- amoxapine (anhedonia)
What are the benefits and risks for using TCAs?
• Benefits ○ Time-tested ○ Very effective ○ Great in severe depression ○ Newer ones have fewer side effects • Risks ○ Hypotenstion ○ Orthostasis ○ Anticholinergic side effects ○ Weight gain ○ Sexual side effects ○ Dangerous in overdose
What are the pros and cons of using MAOIs?
• Pros ○ Can be very effective in non-responsive patients, especially atypical depression ○ Time-tested • Cons ○ Hypotension, orthostasis ○ Dry mouth ○ Constipation ○ Urinary retention ○ Sexual side effects ○ Weight gain ○ Hypertensive crisis (tyramine reaction)
What are the pros and cons of using SSRIs?
• Safe, effective • Multiple indications for use ○ Generalized anxiety disorder ○ Social anxiety ○ Panic ○ OCD ○ PTSD ○ Premenstrual dysphoric disorder • Cons ○ Diarrhea ○ Nausea ○ Jitteriness/anxiety ○ (MAJOR) Sexual side effects (huge here) ○ (MAJOR) Drug interactions b/c of P450 inhibition
What are the pros and cons of using SNRIs?
• Pros ○ Some evidence says these are more effective than SSRIs ○ Safe ○ Better tolerated than TCAs ○ Also used for multiple indications • Cons ○ Sexual side effects ○ Sweating ○ Increased diastolic blood pressure ○ Withdrawal syndrome (flu-like) § "electric shocks"
What are the pros and cons of mirtazapine
- Pros - helpful with insomnia, rapid anti-anxiety effect, low incidence of sexual side effects
- Cons - daytime somnolence, weight gain
