Antidepressant and Stabilizers

Question 1

Depression

Answer 1

An effective disorder characterized by loss of interest and pleasure in daily activities

Question 2

Symptoms of Depression

Answer 2

Diminished interest in activities
Decreased concentration, indecisiveness
Loss of energy, fatigue
Guilt, Excessive guilt, feelings of worthlessness
Loss or gain of appetite
Sleep insomnia or hypersomnia
Psychomotor
Suicide

Question 3

Tricyclic Antidepressants

Answer 3

Effectively relieve depression with anxiolytic and analgesic action
Pharmacologic Properties
- Block presynaptic NE reuptake transporter
- Block presynaptic 5-HT reuptake transporter
- Block reuptake histamine transporter
Block postsynaptic ACh receptor
Have virtually no effect of DA rtransporter
Not selective
Ex. Imipramine(Tofranil), Clomipramine (Anafranil)

Question 4

Effects of Blocking Transporters

Answer 4

ACh blockade leads to dry mouth, confusion, blurry vision, and mental confusion
Histamine blockage leads to drowsiness and sedation
Can induce cardiac depression and increased electrical irritability, can be fatal during/after OD

Question 5

Pharmacokinetics TCA

Answer 5

Well absorbed upon oral absorption
Relatively long half lives
Metabolized in the liver
Converted into intermediates that were then detoxified
Readily crosses the placenta

Question 6

Clinical Limitation TCA

Answer 6

Slow onset of action, 2-4 weeks for antidepressant effect to appear
Wide variety of effects on CNS( adverse effects)- can impair attention, memory motor speed and dexterity
Cardiotoxic and potentially fatal in overdoses

Question 7

Notriptyline

Answer 7

Superior pharmacologic properties compared to all other TCA as psychotropic
Potent as an NRI and has good TI
Safe to combine with MAOI or SSRI
Advantage when treating refractory patients who may require antidepressant drugs

Question 8

Second Generation Trazedone

Answer 8

Not a potent blocker of NE or 5-HT, its active metabolite blocks a class of 5-HT receptors

Question 9

Second Generation Bupropion

Answer 9

Selectively inhibits DA reuptake, used for ADHD

Side effects include nausea, anxiety, restlessness, tremors, insomnia

Question 10

Clomipramine

Answer 10

Sturcutrally a TCA but exerts inhibitory effects on 5-HT reuptake

Question 11

Desmethyclomipramine

Answer 11

Active metabolite, Mixed 5-HT and NE reuptake inhibitor, used to treat OCD, depresion, panic disorder, phobia disorder

Question 12

Venlafaxine

Answer 12

Mxed 5-HT and NE reuptake inhibitor, but also inhibits reuptake of DA and improves psychomotor and cognitive function

Question 13

SSRI

Answer 13

Fluoxetine (Prozac) first released in 1987
Increases the amount of serotonin available to stimulate post synaptic receptors
Can treat depression ADHD, obesity, alcohol abuse, childhood anxiety
Long term- facillitate increased survival and grown of neurons via action on the cAMP response element binding protein and brain derived neurotrophic factor (BDNF)
Reduce glucocorticoids- stress hormone
BDNF lower in depressed patients
Repair neurons, increase neurogenesis, primarily in hippocampal and frontal regions- accounts for the delay in therapeutic response to antidepressant therapy

Question 14

Nefazodone (Serazone)

Answer 14

Unique antidepressant, resembles TCA as an inhibitor of 5HT and NE reuptake, no therapeutic superiority over TCA and SSRI

Question 15

Mirtazapine (Remeron)

Answer 15

Increases noradrenergic and serotonergic neurotransmission by blocking alpha autoreceptors and heteroreceptors, a potent antagonist, rapidly absorbed orally

Question 16

Monoamine Oxidase Inhibitor

Answer 16

1 out of 2 enzymes that break down 5HT and NE
MAO-A inhibition causes antidepressant activity
MAO-B inhibition- causes side effects

Allows more neurotransmitter in synapse
Potential for serious side effects and potentially fatal interactions with other drugs and food

Question 17

Behavioral Therapies

Answer 17

non-pharmacological treatment useful in treating some depression
Number of well controlled studies is limited, so not clear how effective they are long term
More useful when combining pharmacologic therapies
Exersize may also be helfpful
Medications often needed early in the treatment plan, manage overt symptoms
- As symptoms become less intense, more receptive to behavioral therapy
- Medications eventually reduced, behavioral therapies increased
Long term maintenance with low dose is necessary for some

Question 18

Electroconvulsive Therapy

Answer 18

Used for treatment resistant depression
ECT safest quickest most effective treatment for moderate to severe depression
Patient given a muscle relaxer and put under brief anesthesia
Electrical current passed through temples causing a brief seizure

Question 19

ECT Use

Answer 19

begins with several times a week
Shift to weekly, then monthly
Will often also need to take an antidepressant
Given unilaterally on left side, protects memory and cognitive function on right
Electric pulse is briefer and causes fewer side effects

Question 20

ECT Side effects

Answer 20

Confusion
Disorientation
Memory loss
- Mostly gone after treatment
ECT does not cause brain damage, nor permanent dysfunction. Actually increases cerebral functioning of patients with severe dysfunction

Question 21

Repetitive Transcranial Magnetic Stimulation

Answer 21

• Rapidly changing electromagnetic induction used to generate weak electrical currents that are targeted to specific regions of the brain
  Causes both depolarization and hyperpolarization of neurons within current fields
  Modest effect on depression- not as effective as ECT, but side effect profile better

Question 22

Mania

Answer 22

Distinct period of abnormal and persisten elevated expansive or irritable mood
Must last at least 1 week

Question 23

BPD Diagnosis

Answer 23

Distractibility
Indiscretion( Excessive involvement n pleasurable activities with the likelihood of painful consequences)
Grandiosity (Inflated self esteem)
Flght of ideas or racing though
Talkativeness/Pressured speech
Sleep Deficit

Question 24

Hypomania

Answer 24

Same symptoms as bipolar disorder but shorter length of symptoms
Less severe impairment

Question 25

Types of BPD

Answer 25

BPD1- Clear episodes of depression and mania BPD2- less intense and unrecognized manic states Cyclothymia- Chromic moods of hypomania and depression, often evolves into a more serious type Bipolar Disorder Not Otherwise Specified- Largest group of individuals

Question 26

Neurochem of BPD

Answer 26

BPD is progressive neurochemical disorder Regional difference in neuronal density in hippocampus Adrenergic-Cholinergic balance for hypothesis for mania Can have abmormalities in orbitofrontal cortex and amygdala

Question 27

Time Course of BPD

Answer 27

Initial cycle typically MDD Recovery- Relapse Rapid Cycling Rapid- 4 episodes a year Ultrarapid 5-364 Ultraradian > 365 episodes a year

Question 28

Bipolar vs ADHD

Answer 28

Bipolar: More talkative than usual, pressure to keep talking, Distractibility, Increase in goal directed activity, or psychomotor agitation ADHD: Talks excessively, Often easily distracted by extraneous stimuli, always "on the go" as if driven by a motor COMORBID

Question 29

BPD Treatment

Answer 29

Patient can either present with depression or mania Misdiagnosed as unipolar depression or mania Choice of treatment can depend on presentation and severity of disorder Mood stabilizer likely to be more helpful over the long term

Question 30

Mood Stabilizer vs Anti Depressant

Answer 30

Antidepressant can precipitate an episode of mania in BPD and presents with depression first Mood stabilizers reduce cycling between the extreme states Prevent future relapses into mania, mixed, or depressive symptoms

Question 31

Lithium

Answer 31

Historically first effective treatment for bipolar Introduced as sedative hypnotic Significant side effects and blood levels should be monitored Found in natural spring waters Drugs with better side effect profiles are being found Lack of medication adherence Countries with higher levels of lithium in waters have lower levels of depression and suicide

Question 32

Lithium Mechanism of Action

Answer 32

Alters cation transport across cell membrane in nerve cells and muscle cells Influences reuptake of 5-HT and NE Second messenger systems involving phosphaditylinositol cycle are inhibited Post synaptic D2 receptor supersensitivity is inhibited Inhibition of AKT/GSK3 beta signaling

Question 33

Lithium and Grey Matter

Answer 33

Increases gray matter in BPD- areas that regulate attention, motivation, and emotion

Question 34

Lithium Cautions

Answer 34

Take exactly as directed- DONT CHANGE DOSAGE Don't crush or chew tablets Maintain hydration Avoid changes in sodium content- can affect lithium toxicity Limit caffeine intake- diuresis can increase lithium toxicity narrow therapeutic range

Question 35

Carbamazepine (Tegretol)

Answer 35

Effective as lithium, but not as protective | Some patients benefit from taking a combination of the two

Question 36

Valproic Acid

Answer 36

Augments postynaptic action of GABA at its receptors May enhance gene expression in critical brain circuit regions Most effective in acute mania, mixed states, schizoaffective disorders and rapid cycling

Question 37

Gabapentin

Answer 37

Anticonvulsant Relieves symptoms of bipolar disorder, anxiety, certain types of neuropathic pain and substance abuse Similar to valproic acid, except better analgesic GABA analogue and increases intracellular brain GABA levels Excellent PK profile Tolerated, even at high doses Adjunct medicine in patients who are resistant to more effective mood stabiizer, like lithium, valproate or lamotrigine

Question 38

Pregabalin (Lyrica)

Answer 38

Derivative of Gabapentin Approved for treating neuropathies and adjunct to treating partial seizures Not approved to treat BPD

Question 39

Lamotrigine

Answer 39

Not effective in acute manic episodes Often in individuals who are unresponsive to other medications Effective in maintenance and preventing relapse of depressive symptoms

Question 40

Lamotrigine mechanism of action

Answer 40

Inhibits release of excitatory neurotransmitter, glutamate, in cortex and hippocampus Accounts for antiepileptic, antimania and analgesic effects Neuronal excitability is reduced in specific brain regions May also be effective in brain injury patients because of glutamate inhibition

Question 41

Lamotrigine Side Effects

Answer 41

Rash in 1 out of 500 | Stevens-Johnson Syndrome- Epidermal necrolysis- can be fatal

Question 42

Antipsychotic

Answer 42

Effective at treating mania, but little effect on depressive symptoms Atypicals more useful in managing both Olanzapine, risperidone and quetiapine have all had positive clinical trials

Question 43

BPD and Drug Abuse

Answer 43

55% BPD patients also comorbid with drug abuse