Mental Health Flashcards
What is a mental health disorder?
Significant cahanges in a person’s thinking, emotional state and behaviour, and ability to function in social and occupational settings. Meets defined diagnostic criteria
ex. Depression, anxiety, insomnia, bipolar, schizophrenia
How many people experience mental illness?
1 in 5 Canadians will experience mental illness per year
8% will experience major depression in their lifetime
Do most people with mental health issues get help?
No, more than 60% of people with mental health problems and mental illness won’t seek the help they need (stigma is one of the main reasons)
What is the bio-psycho-social model of mental health?
Today mental disorders are primarily seeen as biological disorders of the brain with psychological and social stressors as triggers of episodes of illness
How does culture impact mental illness?
Each culture has a unique perspective on mental health
Culture impacts the way people describe their symptoms
Cultures differ in meaning and level of concern given to mental illness
What is the purpose of the Mental Health Services Act (MHSA)?
Assist people suffering from serious mental illness in recieving treatment
What are two categories of mental health patients recognized by the Mental Health Service Act?
Voluntary (patient has the insight to recognize mental health issue and seeks care)
Involuntary (patient has lost insight to recognize their mental health issue, and must be admitted by a physician or apprehended by authorities)
What is the involuntary admission criteria?
All three criteria must be met including:
1. Being found to be a person with a mental disorder who needs inpatient care
2. Not being fully capable of making an admission or treatment decision
3. Likely to harm or others or suffer substantial mental or physical deterioration
Can non-mental health treatments be given by force to involuntary mental health patients?
No, only mental health conditions can be treated without patient consent
Can pyschologists prescribe medications for their patients?
No, only psychiatrists (MD) can prescibe drugs for mental health patients
Is psychiatry a very subjective field of healthcare?
No, it is very objective
Treatment is often based on the clinicians impressioon of the patient’s thoughts and feelings
What is the DSM-5?
Handbook used in the United States and much of the world as the guide to diagnose mental disorders and is often used in conjuction with clinical judgement
What is the purpose of a clinical psychiatric interviews?
To collect information about the revealed (behavious, intentions, prospects) as well as concealed (emotions, drives, conflicts) aspects of the interviewee’s world
What are the types of questions asked in a clinical psychiatric interviews?
- Patient demographics
- Cheif complaint
- History of presenting illness
- Medical History
- Family Psychiatric history
- and so many more (review slides 47-48)
What are the components of the Mental Status Exam (MSE)?
General Observations
Thinking
Emotion
Cogniton
What are the subcomponents of the general observations section of the Mental Status Exam (MSE)?
- Appearance
- Speech
- Behaviour
- Cooperativeness
What are the subcomponents of the thinking section of the Mental Status Exam (MSE)?
- Thought processes and form
- Thought content
- Perceptions
What are the subcomponents of the emotion section of the Mental Status Exam?
- Mood (patient reported)
- Affect (Interviewer reported)
What are the subcomponents of the cognition section of the Mental Status Exam (MSE)?
- Orientation/Attention
- Memory
- Insight/Judgement
What is a commonly used suicide risk assessment guideline?
The Columbia Protocol (C-SSRS), supports suicide risk assessment via a series of simple, plain-language questions that anyone can ask
What is measurement-based care (MBC)?
Refers to the systematic use of measurement tools, such as validated scales, to monitor outcomes and support clinincal decision-making (such as diagnosis and treatment)
What are some limitations of measurement-based care?
Patients can give false answers that can result in a intended outcome of ill and not ill
What are some concerns about the classification of psychotropic drugs?
They are arbitrarily based on indications the medications were first discovered to treat (based on an earlier period of scientific understanding). As a result differences exist between drugs with current classifications.
This can complicate treatment decision for HCPs
What are the four distinct components of stigma?
- Labelling someone with a condition
- Stereotyping people who have that condition
- Creating a division (creating superior us vs. inferior them)
- Discriminating against someone on the basis of their label
What is the consequence of stigma about mental health conditions?
The fear of stigma often delays diagnosis and treatment, yet early intervention can make a dramatic difference in quality of life
How can we reduce stigma about mental health conditions?
Requires a change in behaviours and attitudes towards acceptance, respect, equitable treatment of people with mental health problems and mental illnesses
What is mental health first aid (MHFA)?
The help provided to a person developing a mental health problem or experiencing the worsening of a mental health problem
What is the 5 step action plan for mental health first aid?
- Assess for risk of suicide or harm
- Listen nonjudgementally
- Give reassurance and information
- Encourage appropriate professional help
- Encourage self-help and other support strategies
What is the definition of major depressive disorder?
Persistently and abnormally low mood, characterized by feelings of sadness, emptiness, or irritability, and accompanied by other somatic or cognitive changes that significantly affect the individuals’s capacity to function.
How many people develop depression?
Globally: 11-18%
Canada: 4-5% (only 63% sought help)
What are some physical health consequences of depression?
- Increased CVD risk and death from CVD conditions
- Increased complications from other medical conditions
- Impaired quality of life
- Impaired social and occupational functioning
What is the onset of depression?
- Average age of onset is late 20s (can occur at any age, but sharp increase between ages 12-16)
- Increases up to early 40s
- May occur after significant life stressor
What is the etiology of depression?
Complex, multifactorial (developmental, biologic, environmental/psychosocial)
Genetic (40-50% inheritable)
Neurobiological (CNS structural damage, chemical abnormalities) or endocrine abnormalities
What are the main hypothesis for the pathophysiology of depression?
- Monoamine hypothesis:
a. Dysfunction in monoamine production (low 5HT = depression) - Neuroplasticity hypothesis:
a. Altered cell growth and adaptation (lower levels of BDNF reduces survival of neurons, and important for structural integrity & neuroplasticity - Endocrine and immune system abnormalities (increased plasma cortisol, cytokine concentrations)
- Structural and functional alterations in brain regions associated with emotional processing (reduced volume or hyperactivity in prefrontal cortex, hippocampus, amygdala)
Is the pathophysiology of depression well understood?
It is complex and not completely known
What are some risk factors for major depressive disorder?
- Genetics
- Life experiences
- Personality Disorders
- Substance Use
- Medical Comorbidities
Review slide 18 for the diagnostic criteria for major depressive disorder
What are the minimum criteria for major depressive disorder diagnosis?
- At least 5 symptoms
- At least 1 symptom must be depressed mood or anhedonia
- Present nearly everyday for at least a 2 week period
- Symptoms cause clinically significant distress or impairment in social, occupational. or other areas of functioning
- Episode is not attibutable to direct physiologic effects of a substance of another medication
- MDD is not better explained by a different mental illness
- There has never been a manic or hypomanic episode
What is persistant depressive disorder?
- Depressive mood for more than 2 years with symptom free period of no longer than 2 months
- More than two additional depressice symptoms (not full criteria for MDD)
What is substance/medication induced depressive episode?
- Prominent, persistant disturbance in mood predominates the clinical picture with diminshed interest in almost all activities
- Symptoms develop during or shortly after substance intoxication or withdrawl and the substance is known to cause disturbance
What are some disorders that may present like depression?
- Bipolar depression
- Anxiety
- Other medical conditions (thyroid abnormalities, anemia, auto-immune)
What are some emotional states that are similar to depression?
- Grief
- Premenstrual syndrome
- Irritable
- Feeling sad
Can prescribed drugs cause depression?
Yes, especially the following:
1. Anti-convulsants (phenobarbital or topiramate)
2. Chronic use of corticosteroid
3. Immunologic agents
What are some signs of behavioural signs of depression?
- Patient may present with poor hygiene, changes in weight, social isolation
- No laboratory tests or imaging studies are available to confirm diagnosis
How can the severity of depression be gauged?
Standardized Rating Scales can be used to make a somewhat objective evaluation of depression symptoms
ex. PHQ-9
What is the relationship between suicide and depression?
Patients with major depressive disorder are at increased risk for suicide (especially if depression is left untreated)
20% of people with untreated depression commit suicide
What are some suicide risk factors?
IS PATH WARM is a good mnemonic
I deation
Substance use
Purposelessness
Anxiety
Trapped
Hopelessness
Withdrawl
Anger
Recklessness
Mood
What is the prognosis for depression?
- 40% recover within 3 months, 60% within 6 months, 80% within 12 months
15% never acheive remission
What is the response to anti-depressants?
Similar to placebo (40-60%)
Some response typically seen within first 2 weeks; peak clinical effect usually 4-6 weeks, may take up to 12 weeks
What are the recurrence rates for depression?
25-50% recurrence within 2 years, 50-80% have more than one episode in lifetime
What are the clinical stages of depression recovery?
Often considered a chronic disease, but patient can see symptom-free periods
- Response (placebo or anti-depressant shows effect)
- Relapse (return to depressive state in less than 12 weeks of last episode)
- Remission (escape depression for longer than 12 weeks)
- Recurrance (become depressed after more than one year)
What are different types of depression clinical status?
- Partial remission (continued presence of some symptoms but full criteria not met)
- Full remission (Absence of significant symptoms)
- Recovery (Full remission for at least 2 months)
- Relapse (New episode before acheive recovery)
- Recurrence (New episode any time after acheiving recovery)
- Chronic (Full criteria for MDD met for a minimum of 2 years
- Treatment Resistance (episode has failed to respond to 2 separate trials of different anti-depressants)
What are some demographic factors that are associated with greater of remission rates?
- Female sex
- Higher income
- Higher level of education
- Employment
- White race
What are some consequences of failing to acheive depression remission?
- Physiological changes to brain
- Increased relapse rates
- Use of medical services
- Increased mortality and suicide attempts
- Review slide 41
What is the overall goal of therapy for depression?
Acute:
Symptom remission and restoration of pre-morbid functioning within 8-12 weeks
Maintenance:
Prevent recurrence of mood episode
What are some initial assessment steps for depression treatment?
- Complete history
- Physical exams & labs
- Mental status exam and suicide risk assessement
- Current medications and substance use
- Past psychotropic meds used (if any)
- Identify target symptoms, treatment preferences, and goals of treatment (improved adherance and efficacy)
- Develop safety plan
- Support education and self-management
What are some non-pharmacological treatments for depression?
- Positive lifestyle changes (long-term and can reduce risk of depressive episodes)
- Natural products (St Johns Wort)
- Psychological treatment (self-help, counselling, psychotherapy)
- Neurostimulation
What are some pharmacological treatments for depression?
- Anti-depressants
- Adjunct drugs
What is a good treatment strategy for mild depression?
Psychological alone is reccomended for mild depression
What is a good treatment strategy for moderate to severe depression?
Pharmacological and Psychological+Pharmacological are often used in moderate to severe cases
What are some examples of psychological treatments?
- Cognitive behavioural therapy
- Behavioural activation
- Interpersonal psychotherapy
- Mindfulness-based cognitive therapy
What is transcranial magnetic stimulation (TMS)?
- Used for refractory despression
- Magnetic fields are used to stimulate nerve cells in regions of the brain involved in mood regulation and depression
- Course: 4-6 weeks
- Adverse effects: headache, scalp discomfort
What is electroconvulsive therapy (ECT)?
- Used for severe depression, depression with psychosis, or catatonic features, severe suicidal ideation
- Induces seizures for 1 min via electrical charge (patient is under general anesthetic)
- 6-12 treatments over 10-14 days
- 80-90% effective
What are some contraindications for electroconvulsive therapy?
- Anticonvulsive dose
- Lithium use
- Bupropion
Are any of the pharmacological treatments better than the others?
No strong evidence to suggest one treatment option being better than the other
What is the best approach to starting on pharmacological agents for depression?
Individualize therapy (need to try different agent to truly find the best medication for each patient’s unique situation
But SSRIs are often started for initial treatment for less severe MDD
What antidepressants are best suited for initial treatment?
The following antidepressants have shown the best balance between efficacy and tolerability:
- Sertraline
- Escitalopram
- Vortioxetine (pricey)
- Venlafaxine (high withdrawl symptoms)
- Mirtazipine (weight gain concern)
What happens to remission rates following subsequent treatment phases?
It steadily declines from more than 30% during earlier steps to close to single digits by the fourth attempt
This shows that is much more difficult to treat someone with more severe forms of depression
What is the probability of long-lasting recovery following antidepressant treatment?
Low, only 7.1% of patients treated did not relapse at 12 months
So keep expectations low and explain to patient they may need to try multiple agents before one sticks
What are some third line agents for depression (often used in treatment resistant depression)?
- Augment with other antidepressant or different med (lithium, TCAs, MAOIs, and ketamine)
- Neurostimulation monotreatment or in combo with other treatments
- Adjunctive acupuncture
Review slide 88 for a table of all drugs used for treatment of depression (contains 1st, 2nd, and 3rd line options)
What are some characteristics of first-line depression agents?
All are SSRIs/SNRIs + bupropion (nicotine direct receptor inhibitor)
What are some characteristics of second-line depression agents?
Older meds
TCAs, Levomilanacipran (SNRI), Moclobemide(reversible MAOI), quetiapine (antipsychotic), Trazodone and Vilazadone
What are some characteristics of third-line depression agents?
Irreversible MAOIs (lots of drug and food interactions)
How do anti-depressants work generally?
They utilize the monoamine hypothesis (try to increase low monoamine levels)
The monoamine hypothesis is controversial, but anti-depressants still work in some patients and situations
What are the the four classes of first-line anti-depression agents?
- SSRIs
- SNRIs
- NDRIs
- a2/serotonin antagonist
What SSRIs are available in Canada?
Citalopram
Escitalopram
Fluoxetine
Paroxetine
Sertraline
What is the mechanism of action for SSRIs?
Inhibition of presynaptic serotonin reuptake by inhibition of the serotonin transporter CNS neurons (increased serotonin in synaptic cleft)
What does the onset of effect in SSRIs look like?
First few days: decreased agitation, anxiety, improved sleep and appetite
First 1-3 weeks: increased activity and sex drive, improved self-care, concentration
2-4 weeks: Relief of depressed mood, return of experiencing pleasure (real effect starts now)
What are some common side effects associated with SSRI use?
HANDS is a good mnemonic
Headache
Anxiety
Nausea
Diarrhea & other GI upset
Sleep disturbance
Also anticholinergic effects are also possible due to muscarinic or NE effects (dry mouth, constipation, blurred vision)
Sexual Dysfunction (male and female): reduced libido, arousal, orgasm
Flat affect
What is a notably serious adverse event associated with SSRI use?
Syndrome of Inappropriate Anti-Diuretic Hormone (SIADH)
SSRIs can trigger this syndrome, causing the kidneys to slow down urine production (leading to buildup of blood volume)
Can cause pain, vomitting, CNS injury, inflammation
What are some monitoring tips for SSRI use?
- Increased risk of suicide (especially in people under 24)
- Increased fracture risk and decreased bone mineral density
- Citalopram, escitalopram, have dose-dependent risk of QTc prolongation
What anti-depressant agents have the greatest acceptibility?
Escitalopram and sertraline have better acceptability
What are some notable examples of CYP450 drug interactions involving SSRIs?
CYP450 DI
Fluvoxamine (CYP1A3)
Fluoxetine & Paroxetine (CYP2D6)
know the above for the exam
What some non-CYP drug interactions involving SSRIs?
NSAIDs, antiplatelets, anticoagulants (increased bleeding risk secondary to decreased platelet aggregation)
Serotonergic agents (increased risk of serotonin syndrome)
What is vortioxetine?
It is an SSRI that also has mixed receptor activity
It also have fewer drug interactions compared to other SSRIs
Review slide 117 for an overview of SSRIs
What SNRIs are available in Canada?
- Venlafaxine
- Duloxetine
- Desvenlafaxine (not on formulary)
What is the mechanism of action for SNRIs?
Inhibit presynaptic serotonin and norepinephrine by inhibiting serotonin and epinephrine transporters in CNS neurons
Thought to be more antidepressive and pro-cognitive than SSRIs
What are some interesting characteristics of Venlafaxine?
It is an SNRI
Binds to serotonin receptors at lower doses (under 150mg/day), and binds to NE and serotonin receptors at relatively higher doses (above 150mg)
At especially high doses (over 450mg/day, venlafaxine will weakly bind to dopamine receptors)
What does the onset of action for SNRIs work?
First few days: Decreased agitation and anxiety (more in SNRIs due to increase in NE)
First 1-3 weeks: Increased activity and sex drive
2-4 weeks: Relief of depressed mood, return of experiencing pleasure
What are some adverse effects associated with SNRI use?
Similar to SSRIs
- HANDS mnemonic
- Anticholinergic-like effects
- Sexual dysfunction
- SIADH
- Risk serotonin syndrome
- Increased BP/HR and sweating
- No sign of increased risk of fractures
- May have less emotional blunting vs. SSRIs
What are some CYP drug interactions involving SNRIs?
Duloxetine and Venlafaxine are moderate to weak inhibitors of CYP2D6 respectively
What are some non-CYP drug interactions involving SNRIs?
NSAIDs, antiplatelets, anticoagulants (increased bleeding risk due to decreased platelet aggregation effects due to serotonin reuptake inhibition)
Serotonergic agents (increased risk of serotonin syndrome)
What are some warnings for SNRI use?
- Duloxetine is contraindicated in narrow angle glaucoma
- Increased risk of suicide in under 24 years old
- Monitor for increased BP
- Caution use if patient has HTN or narrow angle glaucoma
- Duloxetine (avoid in hepatic impairment and risk of urinary retention)
Review slide 128 for comparisons between SNRIs
What NDRI (Norepinephrine and Dopamine Receptor Inhibitor) are available in Canada?
Bupropion is the only one available in its class.
What is the mechanism od action for Bupropion?
It inhibits NE and dopamine transporters increasing concentrations in the synapses
NO serotonin effects (unlike SSRIs and SNRIs)
What is the role of Bupropion in depression therapy?
- Useful for patients with psychomotor retardation, hypersomia, ADHD type symptoms
- Used to augment SSRIs and SNRIs in treatment resistant cases
- Much less risk of sexual dysfunction, and in some cases may alleviate symptoms when using as adjuct
What are some adverse events associated with bupropion use?
Activating (agitation, insomnia, tremor, and anxiety)
Sweating (due to NE reuptake inhibition)
Reduced appetite/weight loss (avoid in eating disorders and increased risk of seizures)
GI upset
Psychosis/exacerbation of psychosis
How is bupropion eliminated by the body?
- By the liver (CYP2B6) and forms active metabolite
- Eliminated by the kidneys (reduced if patient has renal dysfunction)
What are some drug interactions associated with bupropion?
Avoid NRT therapies while on bupropion
Concurrent MAOI therapy
Potent CYP2D6 inhibitor
What are some contraindications for bupropion?
- Seizure disorder
- Eating disorders
- Abrupt discontinuation of alcohol or sedatives
What is the main warning for bupropion use?
Increased risk of suicide if patient is under 24
What a2/serotonin antagonists are available in Canada?
Only Mirtazapine
What is the mechanism of action for Mirtazipine?
Provides moderate peripheral alpha-adrenergic and muscarinic receptor antagonism
Clinical effect is unclear
What is the role of Mirtazipine in depression therapy?
- Used as monotherapy and adjunctive treatment
- Consider in patients with insomnia, anxiety, reduiced appetite
- Benefit for antipsychotic induced akathisia
What are the adverse events associated with mirtazipine?
CNS (Sedation)
Endocrine (Increased triglycerides and weight gain)
Genitourinary (significantly less sexual dysfunction vs SSRI/SNRI)
What are some CYP drug interactions associated with Mirtazipine?
Extensively metabolized by A wide range of CYP enzymes
75% renally excreted
What is the main warning for mirtazipine use?
Increased suicide risk in patients under 24
Caution for hyponatremia in elderly patients
What are the six classes of second-line anti-depressant drugs?
- TCAs
- SNRI (Levomilnacipran)
- Reversible MAOI (Moclobemide)
- Serotonin reuptake inhibitor (Trazodone and Vilazodone)
- Atypical antipsychotic (Quetiapine)
What TCAs are available for sale in Canada?
Tertiary amines:
- Amitriptyline
- Clomipramine
- Doxepin
- Imipramine
Secondary amines:
- Nortriptyline (Aventyl)
- Desipramine
What is the mechanism of action for TCAs?
Inhibit serotonin and NE reuptake by inhibiting serotonin and NE transporters in CNS neurons
Tertiary amines have more serotonin activity
Secondary amines have more NE activity (better tolerated)
Why are TCAs termed the dirty antidepressants?
Individual TCAs have carying affinity got other receptors besides serotonin and NE,
ex. adrenergic, histamine, muscarinic, sodium channels (Na+ channel activation from overdose can be fatal)
What is the role of TCAs in depression therapy?
Treat MDD with the following:
- Insomnia
- Anxiety
- Chronic, non-cancer pain
- Migraines/headaches
- OCD
When are TCAs contraindicated?
- Acute MI, heart block, CHF
- Severe liver impairment
Caution in the following situations:
- Any CVD
- Suicidal ideation
- QT prolongation
- Seizure history/risk
- Elderly
What are some common side effects seen with TCAs?
Sedation, anticholinergic effects, CV
CV is especially important because overdose of TCAs can be lethal due to cardiotoxicity
- Weight gain
- Sexual dysfunction
- Urine discolouration
- Rash
What is the mechanism of action for Trazodone?
Antagonist at alpha-1 adrenergic receptors and H1 histamine receptors (+ dirty antidepressants effects)
Weak inhibition of SERT and NET
What are some side effects associated with Trazodone?
CNS:
- Dizziness
- Sedation
- Headache
CV:
- orthostatic hypotension
- prolonged QT interval, arrythmias
GI:
- Nausea, constipation, dry mouth
Rare:
- Can cause priapism (prolonged erection in 1% of males)
- Sexual dysfunction (less compared to SSRIs/SNRIs)
How is Trazodone eliminated from the body?
Metabolized into active metabolites by CYP3A4
75% excreted via kidney
What are some drug interactions associated with Trazodone?
CYP3A4 inducers and inhibitors
Antihypertensives (dose adjustments may be required since trazodone may cause hypotension due to alpha 1 antagonism
What atypical antipsychotics are available in Canada?
Quetiapine is the only availabile agent in its class
What MAOIs are available for sale in Canada?
Reversible MAOI:
- Moclobemine (favours MAOa over MAOb)
Irreversible MAOI (favours both MAOa and MAOb):
- Selegline
- Phenelzine
- Tranylcypromine
What is the mechanism of action for Moclobemide?
Short-acting reversible inhibitor of MAOa to reduce metabolism of serotonin, NE, dopamine
What happens to doses of Moclobemice above 600mg/day?
Moclobemide looses its specificity for MAOa, will bind to MAOb at this elevated dose
What is the Tyramine Reaction?
This is a drug interaction associated with MAOa inhibition.
MAOa inhibitors prevent metabolism of Tyramine, causing it to build up in the body. This buildup of tyramine promotes the release of NE, causing a hypertensive crisis
Therefore, whenever patient is taking a MAOa inhibitor, caution them from eating tyramine-rich food like cheese, wine, meats, chocolate, etc.
How is Moclobemide eliminated?
Metabolized by CYP2C19 (major) and CYP2D6 (minor)
95% is excreted in the urine as metabolites
How should Moclobemide be initiated if patient is already on a sertronergic drug?
Stop previous serotonergic drug 2 weeks in advance of starting Moclobemide (helps prevent hypertensive reaction or serotonin syndrome)
Same applies if switching from Moclobemide to another antidepressant
If patient on Moclobemide and need to use anesthesia for an operation, when should they do?
Stop Moclobemide for at leasr 2 days prior to local or general anesthesia
What are some adverse effects associated with Moclobemide?
- Tachycardia
- Hypotension
- Sleep disturbances, agitation, nervousness, anxiety
- N/V/D, sexual dysfunction, and anti-cholinergic effects (less frequent than SSRIs/SNRIs)
What Irreversible MAOIs are available for sale in Canada?
Phenelzine
Tranylcypromine
What is the duration of action of irreversible MAOIs?
2-3 weeks
What situations are irreversible MAOIs contraindicated?
- Pheochromocytoma (cells that are releasing sympathetic molecules)
- Concurrent use of serotonergic or sympathomimetic agents
- Tyramine containing food
What is ketamine?
It is a NMDA antagonist that is often used as a third line agent for depression treatment
Ketamine also serves as an agonist at the opioid and AMPA receptors
What is the Chronic Stress Theory for Ketamine?
Ketamine can relieve stressed neurons and improve neural networks (double check this info)
What type of ketamine is commercially available in Canada?
Racemic ketamine (mixed R and S configurations) is commercially available in Canada; approved indication = anesthesia
What configuration of ketamine is most potent as an anti-depressant?
R-ketamine (more potent, longer lasting, with fewer side effects)
What are some safety concerns associated with ketamine use?
Psychiatric (dissociation, psychomimetic)
Neurologic/cognitive
Genitourinary
Hemodynamic effects
What are some common side effects seen with ketamine adminstration?
- Dissociation (out of body experience)
- Dizziness, feeling drunk
- Sedation
- Increased blood pressure
What are the different types of adverse events experienced when on antidepressants?
- Nausea and stomach upset (17-26%)
- Diarrhea (often transient and self-limiting)
- Constipation (drying due to anti-cholinergic effects, paroxetine and TCAs in particular)
- Increased suicidality
How can nausea symptoms following anti-depressant use be managed?
Strategies to mitigate:
- Divide doses/reduce SSRIs if a patient stable
- Take the medication with small amount of food
- Ginger-containing food or beverage (reason unknown)
How do different types of anti-depressants have an impact on development of nausea symptoms?
Venlafaxine and SSRIs are the worst offenders, while Mirtazipine is associated with less nausea due to histamine receptor activation (dirty antidepressant)
How can diarrhea symptoms following anti-depressant use be managed?
- Self-limiting (will go away without intervention)
- Can use anti-diarrheal (loperamide)
- May wish to try probiotics and/or psyllium
How can constipation symptoms following anti-depressant use be managed?
- Self-limiting (goes away within 3 months)
- Adequate activity, fiber
- OTC/self-care as normal
How serious is the concern about the relationship of suicidality and starting on antidepressant therapy?
The FDA currently has a warning for the increased risk of suicidality during initial therapy (first 1-2 months) with any antidepressants (especially for patients between 18-25)
What is the impact of antidepressants on suicidal ideation?
18-24 (increased suicidality)
25-64 (neural protective action has neutral or protective effect on suicidality)
65+ (anti-depressants may have a protective against suicidality relative to placebo)
How are symptoms of suicidality managed?
- Consider hospitalization for patients reporting suicdal ideation, plans, or attempts
- Closely monitor for suicidality in children and youth being newly prescribed antidepressants
- Consider CBT (cognitive-behavioural therapy) or other forms of psychotherapy in patients with suicidality
- For patients that develop suicidality during treatment, consider dose reduction, switching or discontinuing offending agent
What is the impact of anti-depressants on sexual dysfunction?
Sexual side effects can be as high as 70%
SSRIs, TCAs, SNRIs all pose greater risk for sexual dysfunction, while bupropion, mirtazipine, moclobemide poses the lower risk
How can sexual dysfunction caused by antidepressants be managed?
- No intervention (may increase risk of non-compliance)
- Reduce dose (potential disadvantage = relapse)
- Drug holidays or eliminating doses before sexual intercourse (potential disadvantages = withdrawal side effects, increased patient non-adherance)
- Using other medications to augment sexual dysfunction (bupropion or mirtazipine) or (sildenafil or tadalafil for men)
- Switching antidepressant (switch to agent with lower rates of sexual side effects like bupropion)
What is the preferred management strategy for dealing with antidepressant-induced sexual dysfunction?
Switching antidepressant is used most often.
But ultimately, selection of management strategy should be based on patient variables
What class of antidepressant has the highest risk of QT prolongation?
TCAs are high risk especially at higher doses
Cital, escital, venla, mirtaz also have potential to cause QT prolongation
Whenever deciding to put patient on TCAs, get baseline ECG (should be below 440ms) to determine appropriateness
What is serotonin syndrome?
Usually caused by concomitant use of multiple serotenergic agents (ex. SSRI + St. John’s Wort)
Classically described as a triad of the following:
- Mental status changes
- Autonomic hyperactivity (increase in HR/BP, sweating)
- Neuromuscular abnormalities (myoclonic jerking movements)
What is discontinuation syndrome?
This is the withdrawl symptoms associated with anti-depressants. It is common to experience these symptoms (30-50%)
Paroxetine and venlafaxine are the worst offenders (have higher affinity for serotonin transporter)
What are some symptoms observed in patients with discontinuation syndrome?
FINISH mnemonic
Flu-like symptoms
Insomnia
Imbalance
Sensory disturbances
Hyperarousal (anxiety and agitation)
Symptoms start 24-72 hours after d/c, but will resolve spontaneously in 1-2 weeks
Good idea to counsel patients going on anti-depressants (longer than 6-8 weeks) about the importance of tapering down dose and discontinuation syndrome
If discontinuation syndrome occurs during taper down of antidepressant, what should be done?
- Consider restarting medication with slower taper
- If slow taper is poorly tolerated (consider substituting fluoxetine)
What is a general monitoring schedule for newly started antidepressants?
Every 1-2 weeks initially
What should pharmacists do when symptoms persist despite antidepressant therapy for longer than 6-8 weeks?
- Switch to alternate first-line agent
- Augment therapy with an alternate mechanism antidepressant, SGA, or psychotherapy
What are some good questions to ask patients that are not responding to antidepressant therapy?
- History of alcohol, smoking or substance use
- Changes to drugs, diet, lifestyle triggering current episode
- Check for abnormal lab values
- How well is patient tolerating drug
- Adherance to therapy
Is initial treatment failure with antidepressants common?
Yes, almost 2/3 will fail to acheive remission with initial pharmacological treatment
In fact, 30% will experience less than satisfactory benefit depite trying 4 different courses of antidepressants
What are some causes for nonresponse to antidepressant?
- Comorbid disorders including substance use
- Inadequate dose and duration
- Incorrect diagnosis
- Non-adherance
- PK and PD factors
- Unaddressed psychosocial or psychological issues
If patient experiences treatment failure with antidepressants, is there an option that is best indicated?
No according to clinical trials none of the antidepressants are better than one another. So pick one based on patient history
There is some evidence to support increased efficacy with augmentation of therapy with quetiapine
What is the definition of treatment resistant depression?
No standard definition, but a working definition is below:
Lack of improvement (more than 20% reduction in depression scores following adequate trials of two or more antidepressants)
Treatment resistant depression is not a subtype of depression, but it is simply on an extreme end of response to therapy in depression
What can be done in treatment resistant depression?
- May switch antidepressant
- May choose augmentation therapy (lithium, quetiapine, thyroid, etc.)
- Combining antidepressants
a. SSRI/SNRI + mirtazapine
b. SSRI/SNRI + bupropion
c. SSRI + TCA (increased risk of serotonin syndrome)
What are some guidelines for switching between classes of antidepressants?
- If going within either SSRI or SNRI, one can directly switch
- If switching drug from different classes, cross-tapering is preferred (taper one down, while taper other up)
- If an MAOI is one othe drug involved in the switch, allow for a washout period before starting new antidepressant
What are the first-line agents for augmentation in treatment resistant depression?
2nd generation antipsychotics
ex. aripiprazole, quetiapine, risperidone
What are the second-line agents for augmentation in treatment resistant depression?
Lithium
Bupropion, mirtazipine
Thyroid T3
What is the role of ketamine as an adjuct therapy in treatment resistant depression?
It is currently experimental, but there is greater evidence to support its use as an earlier option
What is the role of lithium in adjunct therapy of treatment resistant depression?
One of the most investigated augmentation strategy
Should see response by 3-4 weeks
What is the role of thyroid T3 in adjunct therapy of treatment resistant depression?
Used rarely, but it can improve and accelerate anti-depressant effect in studies
Try for 2 weeks
Caution in patients with cardiac insufficiency or elderly
What is the role of atypical antipsychotics as adjunct therapy of treatment resistant depression?
Augmentation with quetiapine, olanzapine, and risperidone lead to significantly higher response and remission rates vs. placebo
What are three distinct phases of antidepression treatment?
- Acute
- Continuation
- Maintenance
What is defined as response to antidepressant therapy?
50% reduction in symptoms after 4 weeks of treatment, continue with optimal dose and reevaluate at 6, 8, and 12 weeks
What is the definition of the continuation phase of treatment with antidepressants?
Antidepressant should continue at the same dosage as required in the acute phase for additional 4-9 months
What is the definition of the maintenance phase treatment with antidepressants?
Duration is indefinite and may be life-long
What are some factors to consider when deciding if patient requires maintenance phase treatment?
- Severe episodes (psychosis, severe impairment)
- Frequent, recurrent episodes
- Difficult to treat episodes
- Presence of residual symptoms (chronic symptoms)
- Comorbid psychiatric or medical conditions
- Psychosocial stressors
- Family history
- Early age at onset
What do symptoms of depression look like in elderly patients?
Often missed, because symptoms make look different vs. adults
Common symptoms:
- Anhedonia (lack of pleasure or interest in things that previously did)
- Cognitive impairment (memory loss)
- Decreased appetite
- Increases irritability
Are elderly patients more likely to experience remission from treatment compared to adult patients?
No, older patients are less likely to acheieve remission
Symptoms may also take longer to respond to treatment (12+ weeks)
Are antidepressant drugs on the BEERS list of drugs?
Yes, SSRIs, SNRIs, TCAs and mirtazipine are on BEERS
These drugs are associated with increased risk of falls, fractures, hyponatremia, hypotension
Use duloxetine, bupropion, and sertraline, as they are better suited to elderly patients
How is depression treated in children/adolescents?
Active monitoring (psychological) rather than treatment right away (unless severe)
No officially indicated agent for patients under 18 in Canada
SSRIs are usually first line (titrate slowly with closer monitoring due to increased suicidality)
Avoid SNRI, TCA
How is depression in pregnancy treated?
For a drug-naive patient without suicidal ideation:
CBT or interpersonal therapy (IPT), either short-term (10-12 weeks) or with open-ended duration
For a patient with a prior histroy of a good response to medication with moderate- to-severe symptoms:
1st line treatment is combination of psychotropic medications and psychotherapy with open-ended duratio
What are the risks of leaving depression during pregnancy untreated?
Untreated, or undertreated, maternal depression poses significant risks to both the mother and child
Risks of stopping pharmcological therapy often outweigh the risks associated with pharmacotherapy
What are the first line pharmacotherapeutic options for treating depression in pregnant women?
SSRIs are first line with most safety for the following:
- Sertraline
- Citalopram
- Escitalopram
What are the first line pharmacotherapeutic options for treating depression in breastfeeding mothers?
Citalopram, nortriptyline, sertraline, and paroxetine are 1st line because they have low-to-undetectable serum concentrations (at therapeutic doses) in breast-fed infants
