Depression Flashcards
What conditions can people with depression suffer from?
People with depression suffer greatly with persistent feelings of hopelessness, dejection, constant worry, poor concentration, a lack of energy, an inability to sleep and, sometimes, suicidal tendencies
What neurotransmitters are believed to be involved in depression?
Serotonin (5-HT), Norepinephrine (NE), Epinephrine (Epi), dopamine (DA), glutamate and acetylcholine (ACh)
What key drugs can cause or worsen depression?
- ADHD medications: Atomoxetine (Strattera)
- Analgesics (Indomethacin)
- Antiretrovirals (NRTIs): Efavirenz (in Atripla), Rilpivirine (in Complera, Odefsey)
- Cardiovascular medications: beta-blockers (especially propranolol)
- Hormones: hormonal contraceptives, anabolic steroids
- Other: antidepressants, benzodiazepines, systemic steroids, interferons, varenicline, ethanol
What assessment is used to diagnosed depression?
Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5)
What is another example of a widely used depression assessment scale?
The Hamilton Depression Rating Scale where the patient rates their symptoms of depression on a numerical scale, and the total score indicates whether or not depression is present
Describe the DSM-5 Criteria
At least 5 of the following symptoms present during the same two week period (must include depressed mood or diminished interest/pleasure): Mood (depressed), Sleep (increased/decreased), Interest/pleasure (diminished), Guilt or feelings of worthlessness, Energy (decreased), Concentration (decreased), Appetite (increased/decreased), Psychomotor agitation or retardation, Suicidal ideation
*M SIG E CAPS
What is necessary to rule out prior to initiating antidepressant therapy?
It is necessary to rule out bipolar disorder prior to initiating antidepressant therapy to avoid inducing mania or cause rapid-cycling (cycling rapidly between bipolar depression and mania)
What should not be used when depression and anxiety occur together?
When depression and anxiety occur together, BZDs should not be used alone; they can worsen and/or mask depression and can be problematic in patients with concurrent substance abuse disorders
What natural products may be helpful for treating depression?
St. John’s Wort, SAMe (S-adenosyl-L-methionine), valerian, or 5-HTP (5-hydroxytryptophan) may be helpful for treating depression
What are some key drug interactions of natural products that may be helpful for depression?
St. John’s Wort, SAme and 5-HTP can increase the risk of serotonin syndrome and should not be used with other serotonergic agents. St. John’s Wort is a broad-spectrum CYP450 enzyme inducer with many significant drug interactions, and it can cause phototoxicity. Valerian can cause sedation
What needs to be assessed prior to and during drug treatment for depression?
Treatment of depression can require one or more trials of medication/s. If a drug does not work after a suitable trial of at least 4-8 weeks, treatment should be reassessed. A thorough patient history is critical; what worked in the past, or did not work, should help guide therapy
How should mild depression be treated?
Mild depression should be treated with psychotherapy (e.g. cognitive behavioral therapy)
How should moderate to severe depression be treated?
Moderate to severe depression should be treated with medication in addition to the option of psychotherapy. The effectiveness of the different antidepressant classes is generally comparable
What should the initial choice of pharmacotherapy be based on?
The initial choice of medication should be based on the side effect profile, safety concerns and patient-specific symptoms. For most patients an SSRI or SNRI is preferred or mirtazapine or bupropion
What should be done if a woman is on antidepressants and wishes to become pregnant?
It may be possible to taper the drug if the depression is mild and she has been symptom-free for the previous six months. In more severe cases, medications may need to be continued
What do the ACOG guidelines recommend for mild depression in pregnancy?
The ACOG guidelines for mild depression in pregnancy recommend psychotherapy first, followed by drug treatment if needed
What is the concern of the initiation of drug treatment in pregnancy?
The risks of adverse outcomes for both the mother and the unborn baby so the risk versus benefit must be considered individually
What drug treatment is often used initially in depression and pregnancy?
SSRIs are often used initially, with the exception of paroxetine, due to potential cardiac effects
What is the risk of use of SSRIs in pregnancy?
There is a warning regarding SSRI use during pregnancy and the potential risk of persistent pulmonary hypertension of the newborn (PPHN)
What are some recommendations of treatment for postpartum depression?
Breastfeeding helps for physical and emotional symptoms, and is considered beneficial for the baby. Drug safety when breastfeeding is essential. SSRIs or tricyclics are generally preferred (with the exception of doxepin). Brexanolone (Zulresso), a C-IV drug, is FDA-approved for postpartum depression. It is given as a continuous IV infusion over 60 hours and can cause excessive sedation
What population is the use of oral nonselective monoamine oxidase inhibitors limited to?
Due to safety concerns, the use of oral nonselective monoamine oxidase inhibitors, such as phenelzine, tranylcypromine and iocarboxazid is restricted to patients unresponsive to other treatments
What is a safety concern of the use of one or more serotonergic medications?
Since many antidepressants increase serotonin levels, serotonin syndrome can occur with the administration of one or more serotonergic medications. The risk is most severe when a MAO inhibitor is administered with another serotonergic medication
What are some symptoms of serotonin syndrome?
Severe nausea, dizziness, headache, diarrhea, agitation, tachycardia, hallucinations or muscle rigidity
What should be done if an antidepressant is being discontinued?
If an antidepressant is being discontinued, it should generally be tapered over several weeks to avoid withdrawal
What are some withdrawal symptoms?
Withdrawal symptoms include anxiety, agitation, insomnia, dizziness and flu-like symptoms
What mediations carry a higher risk of withdrawal symtpoms?
Paroxetine and venlafaxine carry a higher risk of withdrawal symptoms and must be tapered upon discontinuation
What is an exception to the tapering rule?
An exception to this rule is fluoxetine, which self-tapers because of its long half-life
What are some counseling points of discontinuing an antidepressant?
Pharmacists must counsel patients on the risk of withdrawal symptoms and to not discontinue treatment without discussing with their healthcare provider
What is the boxed warning associated with all antidepressants?
All antidepressants carry a boxed warning of a possible increase in suicidal thoughts or actions in some children, teenagers or young adults within the first few months of treatment or when the dose is changed
*MedGuides are required for all antidepressants
How long does it take for antidepressant medications to work?
Antidepressant medication must be used daily, and will take time to work. Physical symptoms such as low energy improve within 1-2 weeks but psychological symptoms, such as low mood, may take a month or longer
What do physicians and pharmacist need to educate with regards to suicide prevention?
Physicians and pharmacists must educate patients, family and caregivers about the risk of suicidality and screen for suicide risk. If a patient reports suicidal ideation, refer the patient to the ED, the suicide hotline or elsewhere for help. If someone has a plan to commit suicide, it is more likely that the threat is immediate
What is the MOA of selective serotonin reuptake inhibitors (SSRIs)?
SSRIs increase 5-HT by inhibiting its reuptake in the neuronal synapse. They weakly affect NE and DA
What are some examples of SSRIs?
Citalopram (Celexa), Escitalopram (Lexapro), Fluoxetine (Prozac), Paroxetine (Paxil), Sertraline (Zoloft), Fluvoxamine IR/ER
What are some contraindications of SSRIs?
Do not use with MAO inhibitors, linezolid, IV methylene blue or pimozide
What is a contraindication specific to Fluoxetine and Paroxetine?
Do not use with Thioridazine
What is a contraindication specific to Fluvoxamine?
Do not use with Alosetron, Thioridazine or Tizanidine
What is a contraindication specific to Sertraline solution?
Do not use with Disulfiram
What is a contraindication specific to Brisdelle?
Pregnancy
What are some warnings associated with SSRIs?
- QT prolongation: do not exceed citalopram 20 mg/day in elderly (> 60 years), liver disease, with CYP2C19 poor metabolizers or on 2C19 inhibitors; do not exceed escitalopram 10 mg/day in elderly
- SIADH/hyponatremia, fall risk
- Bleeding
What are some side effects associated with SSRIs?
- Sexual side effects: decreased libido, ejaculation difficulties, anorgasmia, erectile dysfunction
- Somnolence, insomnia, nausea, dry mouth, diaphoresis (dose-related), weakness, tremor, dizziness, headache
- Osteopenia/osteoporosis, restless drug syndrome (assess whether the onset coincided with initiation of treatment)
Which SSRI is the most activating?
Fluoxetine (take dose in AM)
Which SSRI is most sedating?
Paroxetine, Fluvoxamine (take dose in PM)
When should other SSRIs be taken?
Take dose in the AM; if causing sedation, take in the PM
What are some notes regarding SSRIs?
- All approved for depression and a variety of anxiety disorders, except Fluvoxamine (only approved for OCD)
- All available in solution except Fluvoxamine
- Sertraline is preferred in patients with cardiac risk
- To switch to fluoxetine delayed release 90 mg/weekly from fluoxetine 20 mg daily, start 7 days after last daily dose
Describe the drug interaction of SSRIs and MAO inhibitors
Can cause serotonin syndrome or hypertensive crisis:
- Allow a two-week washout between MAO inhibitors and SSRIs. Fluoxetine is the exception; due to its long half life, a five-week washout period is required if switching from fluoxetine
- Do not initiate in patients receiving linezolid or IV methylene blue due to risk of serotonin syndrome
Which SSRIs have drug interactions with QT prolonging drugs?
QT prolongation most consistently noted with citalopram and escitalopram. Additive QT prolongation risk with SSRIs and other QT-prolonging drugs
What medications used concomitantly with SSRIs can increase bleeding risk?
Increased bleeding risk when used with anticoagulants, antiplatelets, NSAIDs, select natural products (e.g. gingko, garlic, ginger, ginseng, glucosamine, fish oils), thrombolytics
Which SSRIs are CYP2D6 inhibitors and how does it effect doses of other medications?
Fluoxetine, Paroxetine and Fluvoxamine
- Tamoxifen requires conversion to its active form by CYP2D6. Decreased tamoxifen effectiveness occurs with fluoxetine and paroxetine. Venlafaxine is preferred in combination with tamoxifen
- Some antipsychotic drugs are CYP2D6 substrates and may need a lower dose when given in combination with fluoxetine and paroxetine
What medications should not be used with SSRIs?
Do not use with thioridazine, pimozide or cimetidine
What medications should be used with caution with SSRIs?
Caution with drugs that cause orthostasis or CNS depression due to risks of falls
What is an example of an SSRI and 5-HT1A partial agonist?
Vilazodone (Viibryd)
What is an example of an SSRI, 5-HT3 receptor antagonist and 5-HT1A agonist?
Vortioxetine (Trintellix)
What are some contraindications of SSRI combination products?
Do not use within 14 days of MAO inhibitors; do not use with linezolid or IV methylene blue
What are some warnings associated with SSRI combination medications?
Seizures; avoid in patients with seizure history
What are some side effects of SSRI combination medications?
N/V/D, insomnia, decreased libido (less sexual SEs compared to SSRIs and SNRIs)
- Vortioxetene: constipation
What are some notes specific to Vortioxetine?
Decrease dose by 50% when used with strong CYP2D6 inhibitors
What is the MOA of serotonin and norepinephrine reuptake inhibitors?
Serotonin and norepinephrine reuptake inhibitors (SNRIs) have a similar mechanism as SSRIs, in that they increase 5-HT by inhibiting its reuptake in the neuronal synapse. SNRIs also inhibit reuptake of norepinephrine (NE)
What are some examples of SNRIs?
Venlafaxine (Effexor XR), Duloxetine (Cymbalta), Desvenlafaxine (Pristiq), Levomilnacipran (Fetzima)
What are some contraindications of SNRIs?
- SNRIs and MAO inhibitors can potentially cause a lethal drug interaction; hypertensive crisis
- Do not initiate in a patient receiving linezolid or IV methylene blue
What are some warnings associated with SNRIs?
- SIADH/hyponatremia, fall risk
- Bleeding
What are some side effects of SNRIs?
- Similar to SSRIs
- Side effects due to increased NE: increased HR, dilated pupils (can lead to an episode of narrow angle glaucoma); dry mouth, excessive sweating and constipation
- Can affect urethral resistance; caution when using SNRIs in patients prone to obstructive urinary disorders
- Increased BP: risk is greatest with venlafaxine when dosed > 150 mg/day; can decrease dose (use antihypertensive/s or change therapy)
- Osteopenia/osteoporosis, restless leg syndrome
What are some notes associated with SNRIs?
Do not use levomilnacipran with CrCl < 15 mL/min or duloxetine with CrCl < 30 mL/min
What can the combo of SNRIs and MAO inhibitors cause?
Can cause hypertensive crisis or serotonin syndrome if used together
- A washout period is needed if changing between SNRIs and MAO inhibitors; 14 days are recommended
- Do not initiate in patients receiving linezolid or IV methylene blue due to risk of serotonin syndrome
Which medication has additive QT prolongation?
Venlafaxine
Which SNRI is a moderate CYP2D6?
Duloxetine is a moderate CYP2D6 inhibitor. Tamoxifen requires conversion to its active metabolite by CYP2D6. Decreased tamoxifen effectiveness occurs with duloxetine
What is the MOA of tricyclic antidepressants (TCAs)?
Tricyclic antidepressants (TCAs) primarily inhibit NE and 5-HT reuptake. They also block ACh and histamine receptors, which contributes to the side effect profile
What are the two main categories of TCAs and how are they different?
The two main categories are secondary amines and tertiary amines. Secondary amines are relatively selective for NE. Tertiary amines can be slightly more effective, but have a worse side effect profile
What are some examples of TCA tertiary amines?
Amitriptyline, Doxepin, Clomipramine, Imipramine, Trimipramine
What are some examples of TCA secondary amines?
Nortriptyline, Amoxapine, Desipramine, Maprotiline, Protriptyline
What are contraindications of TCAs?
Do not use with MAO inhibitors, linezolid, IV methylene blue, myocardial infarction; glaucoma and urinary retention (doxepin)
What are some side effects of TCAs?
- Cardiotoxicity: QT prolongation with overdose, orthostasis, tachycardia
- Anticholinergic: dry mouth, blurred vision, urinary retention, constipation (taper off to avoid cholinergic rebound), vivid dreams, weight gain, sedation, sweating, myoclonus
What are some important notes of TCAs?
- Low dose amitriptyline is commonly used and generally well tolerated
- Tertiary amines have increased anticholinergic properties and are more likely to cause sedation and weight gain
What are some important TCA drug interactions?
- MAO inhibitors and hypertensive crisis: two-week washout if going to or from a MAO inhibitor
- Additive QT prolongation risk with TCAs and other QT-prolonging drugs
- Metabolized by CYP2D6
What is an example of a dopamine and norepinephrine reuptake inhibitor?
Buproprion
What are contraindications of Bupropion?
Seizure disorder; history of anorexia/bulimia, abrupt discontinuation of ethanol or sedatives; do not use with MAO inhibitors, linezolid, IV methylene blue or other forms of bupropion
What are some warnings associated with Bupropion?
Neuropsychiatric adverse events possible when used for smoking cessation (can include mood changes, hallucinations, paranoia, aggression, anxiety)
What are some side effects associated with Bupropion?
Dry mouth, CNS stimulation (insomnia, restlessness), tremors/seizures (dose-related), weight loss, headache/migraine, nausea/vomiting, constipation and possible blood pressure changes; sexual dysfunction is rare
What are some significant drug interactions associated with Bupropion?
- Do not use multiple formulations of bupropion
- Increased risk of hypertensive crisis with MAO inhibitors. Allow 14-day washout when converting to a MAO inhibitor
What is the MOA of MAO inhibitors?
Monoamine oxidase inhibitors inhibit the enzyme monoamine oxidase, which breaks down catecholamines, including 5-HT, NE, Epi and DA. if these NTs increase dramatically, hypertensive crisis and death can result
What are some examples of MAO inhibitors?
Isocarboxazid (Marplan), Phenelzine (Nardil), Tranylcypromine (Parnate), Selegiline (Emsam)
What are some contraindications of MAO inhibitors?
- History of cardiovascular disease, cerebrovascular defect, headache, hepatic disease, pheochromocytoma
- Do not use with other sympathomimetics and related compounds
- Severe renal disease (isocarboxazid, phenelzine)
What are some warnings associated with MAO inhibitors?
- Not commonly used, but watch for drug-drug and drug-food interactions (if missed could be fatal)
- Hypertensive crisis or serotonin syndrome an occur when taken with TCAs, SSRIs, SNRIs, many other drugs and tyramine-rich foods
What are some side effects of MAO inhibitors?
- Anticholinergic effects (taper upon discontinuation to avoid cholinergic rebound)
- Orthostasis
- Sedation (except tranylcypromine causes stimulation)
- Sexual dysfunction, weight gain, headache, insomnia
What are some contraindications specific to selegiline?
Use with serotonergic drugs, pheochromocytoma
What are some side effects associated with Selegiline?
Constipation, gas, dry mouth, loss of appetite, sexual dysfunction
What medications should be avoided with MAO inhibitors to avoid hypertensive crisis, serotonin syndrome or psychosis?
MAO inhibitors cannot be used with drugs or food that increase concentrations of epinephrine, norepinephrine, serotonin or dopamine
What are some examples of contraindicated drugs that increase serotonin with use with MAO inhibitors?
Linezolid, lithium, tramadol, opioids, St. John’s Wort, SSRIs, SNRIs, mirtazapine, trazodone, triptans, buspirone and dextromethorphan
What are some examples of contraindicated drugs that increase epinephrine with use with MAO inhibitors?
Bupropion, SNRIs, levodopia, linezolid, methylene blue, stimulants used for ADHD and OTC diet pills/herbal weight loss products
What are some examples of contraindicated tyramine-rich foods that increase norepinephrine with use with MAO inhibitors?
Aged cheese, pickled herring, yeast extract, air-dried meats, sauerkraut, soy sauce, fava beans and some red wines and and beers. Food can become high in tyramine when they have been aged, fermented, pickled or smoked
What are methods of separating antidepressants and MAO inhibitors to avoid serotonin syndrome and hypertensive crisis?
- 2 week washout is required between MAO inhibitors and SSRIs, SNRIs, TCAs, Bupropion
- 5 week washout is required when changing from Fluoxetine to MAO inhibitor
What are some other examples of miscellaneous antidepressants?
Mirtazapine (Remeron), Trazodone, Nefazodone
What is the MOA of Mirtazapine?
Has central presynaptic alpha-2 adrenergic antagonist effects, which results in increased release of NE and 5-HT
What are contraindications of Mirtazapine?
Do not use with MAO inhibitors
What are some warnings associated with Mirtazapine?
Anticholinergic effects, QT prolongation, blood dyscrasias, CNS depression
What are some side effects associated with Mirtazapine?
Sedation, increased appetite, weight gain, dry mouth, dizziness, agranulocytosis (rare)
What is the MOA of Trazodone?
Inhibits 5-HT reuptake, blocks H1 and alpha-1 adrenergic receptors
What are some contraindications of Trazodone?
Do not use with MAO inhibitors, linezolid or IV methylene blue
What are some side effects of Trazodone?
Sedation, orthostasis, sexual dysfunction and risk of priapism
What is the MOA of Nefazodone?
Inhibits 5-HT and NE reuptake, blocks 5-HT2 and alpha-1 adrenergic receptors
What is a boxed warning of Nefazodone?
Hepatotoxicity
What are some contraindications of Nefazodone?
Hepatic disease, concurrent use with MAO inhibitors, carbamazepine, cisapride, pimozide or triazolam
What are some side effects of Nefazodone?
Similar to trazodone, but less sedating
What are some key drug interactions of the miscellaneous antidepressant drugs?
- Additive sedation; avoid use of any other sedating medications along with mirtazapine and trazodone
- Mirtazapine, trazodone; additive QT prolongation risk. Use caution with other medications known to prolong the QT interval
- Avoid use with other serotonergic drugs, due to increased risk of serotonin syndrome
- Avoid use with MAO inhibitors due to increased risk of hypertensive crisis
What are some general principles when selecting the best antidepressant?
- The antidepressant selected should incorporate patient-specific information and history
- If an antidepressant was taken at a reasonable dose for 4-8 weeks and did not work well, do not use it again
- Do not choose a treatment that was poorly tolerated in the past
What is preferred treatment for depression for someone who has cardiac/QT risk?
- Sertraline preferred
- Do not choose a QT-prolonging drug/dose
- Watch for additive QT effects when SSRIs, SNRIs, TCAs, mirtazapine or trazodone are used with other QT-prolonging drugs
What is preferred treatment for depression for a smoker?
Bupropion SR is FDA-approved for smoking cessation
What is preferred treatment for depression for someone who has peripheral neuropathy or pain?
Consider Duloxetine
What should be avoided for someone who is taking serotonergic antidepressants?
- Avoid multiple serotonergic medications due to risk of serotonin syndrome
- Increased bleeding risk with anticoagulants, antiplatelets, NSAIDs and some natural products (e.g.gingko, garlic, ginger, ginseng, glucosamine, fish oils)
What antidepressant should be avoided with someone who has a seizure disorder or at risk for seizures?
Do not use bupropion
What is preferred treatment for depression for someone who is pregnant?
- Do not use paroxetine
- Mild to moderate depression: psychotherapy is first-line
- Severe depression: certain SSRIs are first line
What is preferred treatment for depression for someone who has daytime sedation?
- Do not take a sedating drug early in the day
- Activating medications taken in the morning are preferred
What is preferred treatment for depression for someone who has insomnia?
- Do not take an activating drug later in the day
- Sedating medications taken at night are preferred
What is preferred treatment for depression for someone who has sexual dysfunction?
- High risk with SSRIs and SNRIs
- Lower risk with bupropion and mirtazapine
When is someone considered to have treatment-resistant deression?
Depression that does not fully respond to two full treatment trials is considered treatment-resistant
What does the APA guidelines state about when to conclude that a drug is not working?
The APA guidelines state that patients should receive a 4-8 week trial of medication at a therapeutic dose before concluding that a drug is not working
What should be considered if a patient is not improving with regards to their depression?
- Change to a new antidepressant
- Increase the antidepressant dose
- Use a combination of antidepressants with different mechanisms of action
- Augment with buspirone or a low dose of an atypical antipsychotic (agents approved as augmentation therapy with antidepressants are aripiprazole (Ailify), olanzapine + fluoxetine (Symbyax), quetiapine extended release (Seroquel XR) and brexpiprazole (Rexulti). Esketamine (Spravato) is another option
- Augmentation with lithium, thyroid hormone or in some cases, ECT
What are some boxed warnings associated with the antipsychotics?
- Elderly patients with dementia-related psychosis treated with an antipsychotic drugs are at increased risk of death
- Antidepressants increase the risk of suicidal thinking and behavior in children, adolescents and young adults
What are some contraindications of the antipsychotics?
Olanzapine/fluoxetine (Symbax); do not use with MAO inhibitors, linezolid, IV methylene blue, pimozide, thioridazine & caution with other drugs/conditions that cause QT prolongation
What are some warnings associated with antipsychotics?
- Neuroleptic malignant syndrome, tardive dyskinesia (TD), falls, leukopenia, neutropenia
- Multiorgan hypersensitivity reactions with Olanzapine
- Pathological gambling and other compulsive behaviors (aripiprazole)
What are some side effects associated with these antipsychotics?
- Each of these drugs can cause metabolic issues, including dyslipidemia, weight gain, diabetes (less with aripiprazole)
What are some side effects specific to aripiprazole?
Anxiety, insomnia, akathisia, constipation, agitation
What are some side effects associated with Olanzapine?
Sedation, weight gain, increased lipids, increased glucose, EPS, QT prolongation (lower ris)
What are some side effects associated with Quetiapine?
Sedation, orthostasis, weight gain, increased lipids, increased glucose, EPS (lower risk)
What are some side effects associated with Brexpiprazole?
Weight gain, dyspepsia, diarrhea, agitation
What is an example of an NMDA receptor antagonist?
Esketamine (Spravato) C-III
What is a boxed warning of esketamine?
- Sedation and dissociative or perceptual changes, potential for abuse and misuse
- Antidepressants increase the risk of suicidal thinking and behavior in children, adolescents and young adults
What are some notes associated with Esketamine?
Due to risks, only available through a restricted distribution system under the Spravato REMS program
What are some key counseling points of all antidepressants?
- Can cause suicidal ideation
- MedGuide required
- Can take 1-2 weeks to feel a benefit from this drug and 6-8 weeks to feel the full effect on mood
What are some key counseling points of SSRIs?
- Fluoxetine: take in the morning
- Can cause sexual dysfunction and serotonin syndrome
What are some key counseling points of SNRIs?
Increased blood pressure, increased sweating, sexual dysfunction, serotonin syndrome
What are some key counseling points of tricyclics?
Can cause anticholinergic effects and orthostasis
What are some key counseling points of Bupropion?
Can cause insomnia
What are some key counseling points of MAO inhibitors?
- Can cause serotonin syndrome
- Many drug interactions
What are some key counseling points of other antidepresants?
- Trazodone: take at bedtime (can cause priapism)
- Mirtazapine: take at bedtime
