Treating Depression (Cut off for Exam 4) Flashcards
Partial Response
At least a 50% reduction in reported symptoms
Remission
Resolution of symptoms (screens as if no depressive symptoms present)
Pleiotropic
In the context of drug therapy, unanticipated effects (usually beneficial)
Augmentation
Addition of a second or third medication to achieve greater resolution of symptoms
Severity of Depressive Disorder
- Ideally ranked severity mirrors level of functional impairment in everyday life
- Mild: 4 symptoms, at least one core (depressed mood or loss of interest)
- Moderate: 5-6 symptoms, at least one core but likely meets at least 2
- Severe: 6+ symptoms (likely meets all core requirements)
VA Guidelines
- Depression screening recommended for all patients not currently on therapy for depression
- Recommendations vary depending on depression severity
Mild-Moderate Depression Recommendations
- Psychotherapy (strong recommendation): ACT, IPT, CBT, PST, MBCT
- Pharmacotherapy (strong recommendation): SSRI, SNRI, mirtazapine, bupropion
- Partial response: combo of psycho and pharm therapy, alternative monotherapy, augmentation with second medication
Psychotherapy Abbreviations
- ACT: Acceptance and commitment therapy
- IPT: interpersonal therapy
- CBT: cognitive behavioral therapy
- PST: problem-solving therapy
- MBCT: mindfulness-based cognitive therapy
Severe Depression Recommendations
- Use combination of psychotherapy and pharmacotherapy to start
- Consider ECT
Other ECT Indications
- Catatonia
- Psychotic features
- Patient preference
- Pregnancy
- Intolerable SE with medication
- Need for rapid resolution
All Depression Levels Recommendations
- Continue pharm therapy for at least 6 months after achieving remission
- Treat longer, 12 month to indefinitely, if high risk of relapse
- Consider psychotherapy if stopping pharm and patient is at high risk of relapse
Pregnancy + Depression Recommendations
- Use psychotherapy first
- If stable on med before pregnant, weigh risks/benefits of continuing therapy
Elderly + Depression Recommendations
- 65 y.o.+
- Use psychotherapy first
Patients with SAD
-Light therapy
Treatment Resistance Recommendations
- Defined as failure to achieve remission with at least two adequate pharm therapy trials
- Try MAOI or TCA
- Evidence not strong for ketamine
Other/Alternative Treatments for Depression
- Acupuncture, yoga, tai chi, qi gong as mono or add-on therapy (insufficient evidence)
- Exercise and patient education
Herbals/Supplements
- Not enough evidence for Vitamin D or fish oil as monotherapy
- If patient insists, use standardized St. John’s Wort extract
American Psychiatric Association Guidelines
- Greater focus on diagnosis than VA guidelines
- More detail for non-pharm therapies
- Little difference in actual treatment recommendations for any level of depression
The Campbell Method
-Target the greatest number of presenting symptoms
Avoid the most SE
-Maximize the list of comorbid conditions treated
-Minimize polypharmacy
-Work with patient/caregiver on choice of therapy
Options if First Lines Don’t Work
- Consider referral/consult for diagnosis clarification
- Run the usual lists of trouble-shooting: med compliance, drug-drug/drug-food interactions
- Dose titration: not universally accepted process, SNRI/SSRI/atypicals saw no additional benefit from titration
- Switching agents: mixed evidence on best modality
- Augmentation Strategies
Augmentation Strategies
- Second Antidepressant
- Atypical antipsychotics
- Miscellaneous
Second Antidepressant Options
Bupropion
- Can use with SSRI, SNRI, TCA, mirtazapine, or nefazodone
- Best option if experiencing sexual dysfunction with SSRI
- Avoid dosing after 3-4 PM
Mirtazapine
- Best option if also having insomnia or poor appetite
- Lower doses are MORE sedating
Atypical Antipsychotic Options
- Best evidence currently for augmentation with atypical antipsychotics after failing second antidepressant trial
- Usually use lower doses than if treating a psychosis
- Aripiprazole, Brexpiprazole, Olanzapine, and Quetiapine are all options
Aripiprazole
- Least sedating
- Low metabolic risk
Brexpiprazole
- More or less works like aripiprazole with slightly more metabolic SE
- More expensive
- No evidence that it is superior
Olanzapine
-Avoid as initial choice due to worse metabolic complications
Quetiapine
- Usually use IR
- Major active metabolite acts as a potent NE reuptake inhibitor
- Highly sedating
- Orthostatic hypotension common in older adults
- Metabolically less favorable, better than olanzapine though
Miscellaneous Treatment Options
- Lithium
- Liothyronine
- Buspirone
- Pramipexole
- Modafinil
Lithium
- Go to agent for years
- Concerns or renal toxicity with long term use
- Requires biannual monitoring or ECG, renal fxn, CBC, and lithium levels
- Generally well-tolerated at doses used for augmentation
- One or two medications to REDUCE suicide risk
Liothyronine
-Be careful not to induce HYPERthyroidism
Buspirone
-No benefit unless concurrently diagnosed with GAD
Pramipexole
- Reasonable option for targeting apathy and anhedonia
- Nausea (younger patients), orthostatic hypotension (older patients), and history of impulsive behaviors should be monitored
Modafinil
- FDA-approved for augmentation
- Good for excess fatigue and/or apathy
Prophylaxis for SE
- Prevent with proactive counseling
- Switching therapies is usually easiest if SE still occur
SE: Sexual Dysfunction Alternative
- Vague term, clarify exact symptoms with patient/provider
- Erectile dysfunction: sildenafil, tadafil, etc
- Loss of libido/inability to reach orgasm: add bupropion
- Any form of sexual dysfunction: CHANGE medication
- Bupropion, mirtazapine, and nefazodone have lowest rate of sexual dysfunction as monotherapies
SE: Insomnia Alternatives
- Adjust timing of current medication
- Add mirtazapine (7.5 mg) or trazodone (12.5-25 mg) at LOW dose
- Quetiapine (12.5-100 mg) is second-line due to SE
SE: Fatigue Alternatives
- Adjust timing of current medication
- Modafinil
- Bupropion can have a mild stimulant effect
- Methylphenidate, ampehtamines, and aripiprazole are all valid options as well
Serotonin Syndrome
- Can occur from excessive serotonin activity form taking too many serotonergics
- Exceedingly rare
- Treatment: withdrawal of offending agents
- Cyproheptadine also recommended, direct 5HT antagonist
QT Interval Prolongation
- Most every medication prolongs QT to some extent
- Aripiprazole is rare exception: SHORTENS QT interval
- Duloxetine neutral effecton QT inteval and is a good option if baseline prolongation is present
- Effect is additive
- Solution: monitor with regular ECGfs, use caustion is QT > 450 msec, stop/taper meds if QT > 500 msec
smoking
- Aromatic hydrocarbons induce CYP1A2
- Will significantly effect the levels of clozapine and olanzapine
CYP2D6
- Fluoxetine, bupropion, duloxetine, paroxetine are INHIBITORS
- Watch out for use of meds metabolized by this enzyme
Psychotherapy
- Many different forms exist
- CBT is most widely used and studied form
- Can be done face-to-face or in a computer based way
ECT
- Most effect treatment for depressive disorders (70-90% see positive response)
- Safest treatment in existence
- SE: transient anterograde amnesia, permanent retrograde amnesia
- One of the fastest treatments
- Best if 2-3 treatments over 6-12 weeks
- Virtually no CI except Lithium
- Lithium can cause prolonged delirium after procedure, reduce or stop dosing to avoid this SE
- Avoid/taper off most anticonvulsants if possible
Repetitive Transcranial Magnetic Stimulation
- rTMS
- Utilizes brief magnetic pulses directed at specific regions of cerebral cortex
- Pulses delivered repetitively between 10-20 Hz
- Approved for those failing to response to at least one antidepressant
- Response rate is variable
Other Non-Pharm Options
- Animal-assisted therapy
- Yoga
- Tai chi
- Qi gong
- Aerobics
Why won’t I feel better immediately?
- Neurogenesis takes 2-6 weeks to take effect
- Increased neurotransmitters will occur immediately
I’ve heard antidepressants work no better than placebos
- Mild depression tends to have high rates of natural remission
- Moderate to severe depression still sees benefits from antidepressant use
Are antidepressants safe while pregnant?
- SSRIs and septal heart defects are root of public concern
- SSRIs do not appear to have associated congenital heart defects
- Risk of untreated depressant shown to have a larger risk of this defect than SSRIs
- Use during first trimester is the greatest association with risk
Suicide Screening
- ALL health care professionals should ask
- Full risk assessments require qualified providers
- Be blunt: are you considering harming or killing yourself?
- Normalize the situation with facts (10% consider suicide in their lifetime)
Ketamine
- Infusions can be done at facilities and psychiatric offices
- Use lower doses than used for anesthesia
- 40-minutes infusions
- Similar treatment schedule to ECT
Esketamine
- Spravato
- Nasal spray
- Approved for use with oral antidepressants
- Dose: 28-84 mg intranasally
- Requires 2 hours of observation and a driver home afterwards
- Shown to increase time until relapse when taken with antidepressant than when antidepressant is taken as monotherapy
Hydroxynorketamine
- Likely antidepressant metabolite from ketamine
- Enhances AMPA signaling pathway under an unclear mechanism
