week 7- antidepressants

Question 1

major depression

Answer 1

• complex mood disorder often characterized by low mood
• lasts for two or more weeks
• symptoms occur most days for all or most of the day
• more common in women, but gender gap narrows with age

Question 2

etiology of major depressive disorder

Answer 2

no specific cause but thought to be due to genetics, childhood experience, personality and brain chemistry (NT)

Question 3

symptoms of depression

Answer 3

• characterized by depressed or low mood, loss of pleasure/interest in all or almost all of one’s usual activities
• common symptoms include insomnia/hypersomnia, fatigue, feeling unmotivated, agitated, worthlessness/hopelessness
• other symptoms include anorexia, hyperphagia, trouble concentrating, frequent tearfulness
• associated with high suicide risk (women more likely to attempt, men more likely to complete)

Question 4

treatment of depression

Answer 4

• lifestyle changes: healthy diet, aerobic exercise/resistance training
• psychotherapy: CBT to manage negative thoughts
• pharmacology: TCAs, SSRIs, SNRIs, MAOIs, atypical antidepressants
• somatic therapy: ECT, transcranial magnetic stimulation (useful for rapid response when treatments have failed)

Question 5

pharmacotherapy for depression

Answer 5

• limited to severe depression
• five major classes (SSRIs, SNRIs, MAOIs, atypical, TCAs)
• all classes of drugs are equally as effective
• differences are between side effects and drug interaction

Question 6

considerations for all antidepressants

Answer 6

• symptoms resolve slowly
• initial response seen in 1-3 weeks
• full effect seen in up to 12 weeks (cannot consider a drug ineffective until one month, cannot be used PRN)
• dosing starts low and gradually increases
• if not successful, increase dose, switch to drug in same class, switch to drug in different class, add an atypical antidepressant

Question 7

important considerations for initiating antidepressants

Answer 7

• patients with depression may have suicidal thoughts or ideations
• increased risk of suicide early in treatment (more likely in children, adolescents and adults <25)
• observe mood, suicidality and behaviour changes closely
• involve family

Question 8

discontinuing antidepressants

Answer 8

• when symptoms are in complete remission, continue taking drug for 4-9 months
• taper medication to prevent withdrawal symptoms
• slowly decrease medication dosing

Question 9

selective seretonin reuptake inhibitors (SSRIs)

Answer 9

• specific to serotonin (5HT)
• block the reuptake of seretonin from within the synapse
• causes an increase in serotonin (more available in the synapse)
• therapeutic effects are delayed
• alterations from LT serotonin blockade
  ie. fluoxetine, setraline, citalopram

Question 10

uses for SSRIs

Answer 10

• major depression
• bipolar disorder, OCD, panic disorder, premenstrual dysphoric disorder, bulimia nervosa
• off-label uses include PTSD, social phobia, EtOH misuse, migraines, tourette’s syndrome

Question 11

side effects of SSRIs

Answer 11

nausea, headache, CNS stimulation, weight loss then weight gain, sexual dysfunction, bleeding disorders (serotonin is involved in platelet aggregation), increased suicide risk, serotonin syndrome

Question 12

seretonin syndrome

Answer 12

• too much serotonin in the synapse
• leads to altered mental status, poor coordination, tremor, fever, excess sweating, hyperreflexia

Question 13

withdrawal syndrome

Answer 13

• occurs with abrupt discontinuation of SSRI
• begins within days after last dose, lasts 1-3 weeks
• symptoms include dizziness, headache, nausea, sensory disturbances, tremor, anxiety, dysphoria
• symptoms improve with restarting the drug
• important to distinguish depression and withdrawal
• neonatal effects if mother takes SSRI (neonatal abstinence syndrome, persistent pulmonary HT of the newborn)

Question 14

drug interactions with SSRIs

Answer 14

a) thiazide diuretics- can cause hyponatremia
b) other antidepressants- risk of serotonin syndrome
c) antiplatelet and anticoagulant drugs- plasma binding

Question 15

selective NE-serotonin reuptake inhibitors (SNRIs)

Answer 15

• similar to SSRIs, blocks serotonin and NE
• similar uses to SSRIs, also used for pain disorders
• similar side effects, some CV side effects and inc risk of suicide
• much more profound withdrawal symptoms
  ie. dulozetine, venlafaxine, disvenlafaxine

Question 16

tricyclic antidepressants (TCAs)

Answer 16

• block reuptake of serotonin and NE
• can also block histamine and Ach receptors
• used for depression, BPD, fibromyalgia, neuropathic pain and insomnia
• has significant side effects
  ie. amytriptyline, imipramine, doxepin

Question 17

side effects of TCAs

Answer 17

orthostatic hypotension, anticholinergic effects, sedation, cardiac toxicity, seizures, hypomania, increase suicide risk

Question 18

monoamine oxidase inhibitors (MAOIs)

Answer 18

• monoamine oxidase is an enzyme used to breakdown NT
• MAOIs prevent the breakdown of NT
• side effects include anxiety, insomnia, agitation, anticholinergic effects, orthostatic hypotension
• interacts with foods that contain tyramine (avocado, wine, fish, dairy, bananas, yeast)
  ie. phenelzine, isocarboxazid, tranylcypromine

Question 19

ADHD in children

Answer 19

• most common neuropsychiatric disorder in children (5-11% of school children)
• males are 2x more likely
• characterized by inattention, hyperactivity and impulsivity
• many theories on etiology, most involve NE/dopamine/serotonin
• treatment with psychotherapy and pharmacology (benefits of meds diminish in 2-3 years)

Question 20

ADHD in adults

Answer 20

• can persist from childhood in 30-60% of cases
• characterized by poor concentration, stress intolerance, antisocial behaviour, anger, inability to maintain a routine
• associated with increased MVAs, divorce rates and termination of employment
• only 2/3 of adults respond to drugs

Question 21

CNS stimulants

Answer 21

• increase the activity and excitation of CNS neurons
• some suppress neuronal inhibition
• used for ADHD and narcolepsy
• cannot elevate mood without general CNS excitation
• many uses, high risk for abuse

Question 22

amphetamines

Answer 22

• actions within the CNS and PNS
• inhibit mainly dopamine and NE reuptake
• dopamine is responsible for reward, motivation and movement
• NE is responsible for energy, bp and HR
• tolerance and physical dependence can occur
• high potential for abuse
  ie. adderall and vyvanse for ADHD

Question 23

methylphenidate (ritalin)

Answer 23

• structure is different from amphetamines, but MOA is similar
• blocks the reuptake of NE and dopamine
• similar side effects and abuse risk as amphetamines

Question 24

role of CNS stimulants in ADHD

Answer 24

• decrease impulsivity and hyperactivity by improving focus and attention
• don’t create positive behaviour, only diminish negative behaviour

Question 25

abuse potential of psychostimulants

Answer 25

- very high likelihood for abuse - stimulate CNS, heart, blood vessels and sympathetic organs

Question 26

cocaine

Answer 26

- used by 2% of canadians - similar effects to amphetamines (local anesthesia, vasoconstriction) - exists as cocaine (powder) and crack (crystals) - powder is snorted (slow intranasal absorption), crystals are heated and injected (immediate entry into circulation)

Question 27

cocaine mechanism of action

Answer 27

- blocks dopamine reuptake - increases dopamine activation in reward centres of the brain, leading to euphoria - highly lipid-soluble, crossing placenta

Question 28

cocaine toxicity

Answer 28

a) acute toxicity - OD and death are common - mild OD toxicity: agitation, dizzy, tremor - severe OD toxicity: hyperpyrexia, convulsion, ventricular arrythmias, hemorrhagic stroke, coronary vasospasm b) chronic toxicity - atrophy of nasal mucosa - necrosis/perforation of nasal septum - severe lung injury

Question 29

methamphetamine

Answer 29

- white, crystalline powder - can be swallowed, snorted, smoked or injected - use has been increasing in Canada - increases release of dopamine and NE and prevents reuptake - leads to arousal, elevation of mood, euphoria, loquaciousness, increased sense of strength/mental capacity, increased self confidence, no desire to eat or sleep

Question 30

meth adverse effects

Answer 30

a) CNS: delusions, paranoia, auditory and visual hallucinations (resolve with cessation) b) cardiac: vasoconstriction, cardiac stimulation, angina, arrythmias - vasculitis, renal failure and stroke with severe toxicity c) general: weight loss, tooth decay, prolonged cognition and memory defects d) fetal: preterm birth, low birth weight, placental abruption, intrauterine growth restriction, neonatal death

Question 31

stimulant withdrawal timelines

Answer 31

days 1-3: anxiety, paranoia, body aches, fatigue, feeling unwell, hallucinations, trouble sleeping, craving for drug days 4-10: extreme fatigue, significant depression, drug cravings days 11-17: depression, insomnia, mood swings, cravings decrease days 18+: depression and craving may continue

Question 32

tolerance

Answer 32

body needs increasing amounts of the drug to achieve the same effect

Question 33

dependence

Answer 33

body requires the drug to be able to function and feel normal, may experience some withdrawal symptoms without the drug

Question 34

addiction 4Cs

Answer 34

craving, compulsion to use, loss of control, used despite consequences