week 7- antidepressants Flashcards
major depression
- 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
etiology of major depressive disorder
no specific cause but thought to be due to genetics, childhood experience, personality and brain chemistry (NT)
symptoms of depression
- 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)
treatment of depression
- 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)
pharmacotherapy for depression
- 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
considerations for all antidepressants
- 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
important considerations for initiating antidepressants
- 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
discontinuing antidepressants
- when symptoms are in complete remission, continue taking drug for 4-9 months
- taper medication to prevent withdrawal symptoms
- slowly decrease medication dosing
selective seretonin reuptake inhibitors (SSRIs)
- 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
uses for SSRIs
- 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
side effects of SSRIs
nausea, headache, CNS stimulation, weight loss then weight gain, sexual dysfunction, bleeding disorders (serotonin is involved in platelet aggregation), increased suicide risk, serotonin syndrome
seretonin syndrome
- too much serotonin in the synapse
- leads to altered mental status, poor coordination, tremor, fever, excess sweating, hyperreflexia
withdrawal syndrome
- 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)
drug interactions with SSRIs
a) thiazide diuretics- can cause hyponatremia
b) other antidepressants- risk of serotonin syndrome
c) antiplatelet and anticoagulant drugs- plasma binding
selective NE-serotonin reuptake inhibitors (SNRIs)
- 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
tricyclic antidepressants (TCAs)
- 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
side effects of TCAs
orthostatic hypotension, anticholinergic effects, sedation, cardiac toxicity, seizures, hypomania, increase suicide risk
monoamine oxidase inhibitors (MAOIs)
- 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
ADHD in children
- 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)
ADHD in adults
- 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
CNS stimulants
- 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
amphetamines
- 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
methylphenidate (ritalin)
- structure is different from amphetamines, but MOA is similar
- blocks the reuptake of NE and dopamine
- similar side effects and abuse risk as amphetamines
role of CNS stimulants in ADHD
- decrease impulsivity and hyperactivity by improving focus and attention
- don’t create positive behaviour, only diminish negative behaviour
abuse potential of psychostimulants
- very high likelihood for abuse
- stimulate CNS, heart, blood vessels and sympathetic organs
cocaine
- 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)
cocaine mechanism of action
- blocks dopamine reuptake
- increases dopamine activation in reward centres of the brain, leading to euphoria
- highly lipid-soluble, crossing placenta
cocaine toxicity
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
methamphetamine
- 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
meth adverse effects
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
stimulant withdrawal timelines
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
tolerance
body needs increasing amounts of the drug to achieve the same effect
dependence
body requires the drug to be able to function and feel normal, may experience some withdrawal symptoms without the drug
addiction 4Cs
craving, compulsion to use, loss of control, used despite consequences
