Psychopharmacology

Question 1

what are the indications for use of Antidepressants?

Answer 1

Unipolar and bipolar depression, organic mood disorders, schizoaffective disorder, anxiety disorders including OCD, panic, social phobia, PTSD. There is a delay typically of 3-6 weeks after a therapeutic dose is achieved before symptoms improve.

Question 2

list the types of Antidepressants…

Answer 2

Tricyclics (TCAs)
Monoamine Oxidase Inhibitors (MAOIs)
Selective Serotonin Reuptake Inhibitors (SSRIs)
Serotonin/Noradrenaline Reuptake Inhibitors (SNRIs)
Novel antidepressants

Question 3

what are TCA’s side effects?

Answer 3

Very effective but potentially unacceptable side effect profile i.e. antihistaminic (weight gain, sedation), anticholinergic (dry mouth, dry eyes, constipation, memory deficits and potentially delirium), antiadrenergic (orthostatic hypotension, sedation, sexual dysfunction). QT lengthening, lethal in overdose (can overdose on a weeks supply)

Question 4

what do tertiary TCA’s act on? Give egs ontertiary tca’s…

Answer 4

Act predominantly on serotonin receptors

Examples:Imipramine, amitriptyline, doxepin, clomipramine

Question 5

what are secondary TCA’s and what do they act on, give egs too…

Answer 5

metabolites of tertaiary amines, Primarily block Noradrenaline. Eg’s: Desipramine, notrtriptyline

Question 6

What are MAOI’s and list their side effects…

Answer 6

bind irreversibly to monoamine oxidase preventing amine inactivation leading to increased synaptic levels on amines. Side effects:orthostatic hypotension, weight gain, dry mouth, sedation, sexual dysfunction and sleep disturbance

Question 7

when can a hypertensive crisis occur with MAOI’s?

Answer 7

when taken with tyramine-rich foods or sympathomimetics

Question 8

when can a serotonin syndrome occur with MAOI’s?

Answer 8

If you take MAOI with meds that increase serotonin or have sympathomimetic actions. Serotonin syndrome sx include abdominal pain, diarrhea, sweats, tachycardia, HTN, myoclonus, irritability, delirium. Can lead to hyperpyrexia, cardiovascular shock and death. To avoid need to wait 2 weeks before switching from an SSRI to an MAOI.

Question 9

what are SSRI’s and their side effects…

Answer 9

Block the presynaptic serotonin reuptake. Treat both anxiety and depressive sx, Most common side effects include GI upset, sexual dysfunction (30%+!), anxiety, restlessness, nervousness, insomnia, fatigue or sedation, dizziness

Question 10

discontinuation syndrome…

Answer 10

condition that can occur following the interruption, reduction, or discontinuation of antidepressant medication. The symptoms may include flu-like symptoms, trouble sleeping, nausea, poor balance, sensory changes, and anxiety.

Question 11

PROS and CONS of - Paroxetine

Answer 11

P - short half life, no build up, sedating properties (dose at night) gives relief from anxiety and insomnia. C - Sedating, wt gain, more anticholinergic effects Likely to cause a discontinuation syndrome

Question 12

PROS and CONS of - Sertraline

Answer 12

P - weak P450 interactions, short half life, less sedating compared to paroxetine. C - max ab. Requires a full stomach, increase number of GI adr’s

Question 13

PROS and CONS of - Fluoxetine (Prozac)

Answer 13

P - Long half-life so decreased incidence of discontinuation syndromes. Good for pts with medication noncompliance issues. Increased energy. C - long half life and active metabolite may build up (e.g. not a good choice in patients with hepatic illness), Significant P450 interactions so this may not be a good choice in pts already on a number of meds, more likely to unduce mania than other SSRI’s

Question 14

PROS and CONS of - Citalopram

Answer 14

P - Low inhibition of P450 enzymes so fewer drug-drug interactions, Intermediate ½ life. C - Dose-dependent QT interval prolongation, can be sedating anf has GI side effects.

Question 15

PROS and CONS of - Escitalopram

Answer 15

P - Low overall inhibition of P450s enzymes so fewer drug-drug interactions, Intermediate 1/2 life, more effective than citalopram in acute response and remission. C - Dose-dependent QT interval prolongation, nausea and headache.

Question 16

PROS and CONS of - Fluvoxamine

Answer 16

P - shortest half life, analgesic properties. C - short half life, GI side effects, headaches, sedation, weakness, Strong inhibitor of CYP1A2 and CYP2C19

Question 17

what are SNRI’s?

Answer 17

Inhibit both serotonin and noradrenergic reuptake like the TCAS but without the antihistamine, antiadrenergic or anticholinergic side effects. Used for depression, anxiety and possibly neuropathic pain

Question 18

PROS and CONS of - Venlafaxine

Answer 18

minimal drug interactions, short half life and fast renal clearance avoids build up so good for the geriatric population. C - 10-15 mmHG dose dependent increase in diastolic BP, nausea, Can cause a bad discontinuation syndrome, QT prolongation, sexual side effects.

Question 19

PROS and CONS of - Duloxetine

Answer 19

P - efficacy for physical sy of depression, less BP increase as compared to venlafaxine. C - Cannot break capsule, as active ingredient not stable within the stomach, higher drop out rate.

Question 20

Novel Antidepressants: PROS and CONS of - Mirtazapine

Answer 20

P - good augmentation strategy. C - inreases serum cholestrol and TAG’s, sedating, weight gain association

Question 21

Novel Antidepressants: PROS and CONS of - Buproprion

Answer 21

P - good augmentation strategy, Mechanism of action likely reuptake inhibition of dopamine and norepinephrine . C - siezure risk increased, abuse potential because can induce psychotic sx at high doses, anxiety, agitation and insomnia too.

Question 22

CASE 1…

Answer 22

Susie has a nonpsychotic unipolar depression with no history of hypomania or mania. She has depressed mood, hyperphagia, psychomotor retardation and hypersomnolence. What agent would you like to use for her?
Establish dx: Major depressive disorder and target symptoms. For a treatment naive patient start with an SSRI.
Using the side effect profile as a guide select an SSRI that is less sedating. Good choices would be Citalopram, Fluoxetine or Sertraline.

Question 23

CASE 2…

Answer 23

ob is a 55 year old diabetic man with mild HTN and painful diabetic neuropathy who has had previous depressive episodes and one suicide attempt. He meets criteria currently for a major depressive episode with some anxiety. He has been treated with paroxetine, sertraline and buproprion. His depression was improved slightly with each of these meds but never remitted.
Establish dx: Major depressive disorder with anxious features. Assuming he received adequate trials previously would move on to a duel reuptake inhibitor as he had not achieved remission with two SSRIS or a novel agent. Given his mild HTN would not choose Venlafaxine. TCA’s can help with neuropathic pain and depression however not a good choice given the SE profile and lethality in overdose. Duloxetine is a good choice since it has an indication for neuropathic pain, depression and anxiety. Three birds with one stone!! Keep in mind Duloxetine is a CYP2D6 and CPY1A2 inhibitor and has potential drug-drug interactions. Combination of antidepressants eg SSRI or SNRI with Mirtazepine. Adjunctive treatment with Lithium. even ECT if nothing else works.

Question 24

what are indications of use of Mood Stabilisers?

Answer 24

Bipolar, cyclothymia, schizoaffective, Mania

Question 25

name the 3 classes of mood stabilisers…

Answer 25

Lithium, anticonvulsants, antipsychotics

Question 26

what is Lithium and what are the factors predicting a positive response towards it?

Answer 26

Effective in long-term prophylaxis of both mania and depressive episodes. Factors predicting positive response to lithium: Prior long-term response or family member with good response, Classic pure mania, Mania is followed by depression. Only medication to reduce suicide rate.

Question 27

how is its use started and monitored?

Answer 27

Get baseline U&E and TSH. In women check a pregnancy test- during the first trimester is associated with Ebstein’s anomaly. Then monitor usage.

Question 28

side effects of lithium… can be very toxic…

Answer 28

GI distress including reduced appetite, nausea/vomiting, diarrhea, Thyroid abnormalities, Nonsignificant leukocytosis, Polyuria/polydypsia secondary to ADH antagonism. In a small number of patients can cause interstitial renal fibrosis. Hair loss, acne, Reduces seizure threshold, cognitive slowing, intention tremor.

Question 29

anticonvulsants - Valproic acid

Answer 29

better for mania, Before med is started: baseline liver function tests (lfts), pregnancy test and FBC, Start folic acid supplement in women. Thrombocytopenia and platelet dysfunction, Nausea, vomiting, weight gain, Sedation, tremor, Increased risk of neural tube defect 1-2% vs 0.14-0.2% in general population secondary to reduction in folic acid, Hair loss

Question 30

carbamazepine

Answer 30

first line for acute mania and mania prophylaxis, indicated for rapid cyclers and mixed patients, se: rash, Nausea, vomiting, diarrhea, Sedation, dizziness, ataxia, confusion, AV conduction delays, Aplastic anemia and agranulocytosis (<0.002%), Water retention due to vasopressin-like effect which can result in hyponatremia, Drug-drug interactions!

Question 31

Lamotigrine side effects…

Answer 31

Nausea/vomiting, Sedation, dizziness, ataxia and confusion, The most severe are toxic epidermal necrolysis and Stevens Johnson’s Syndrome. The character/severity of the rash is not a good predictor of severity of reaction. Therefore, if ANY rash develops, discontinue use immediately. Blood dyscrasias have been seen in rare cases. Drugs that increase lamotrigine levels: VPA (doubles concentration, so use slower dose titration), sertraline.

Question 32

CASE 3…

Answer 32

33 yo woman hospitalized with her first episode of mania. She has no previous history of a depressive episode. She has no drug or ETOH history and has no medical issues. What medication would you like to start? Given her first presentation was a manic episode statistically she will do better on lithium.
Make sure to check a pregnancy test, serum creatinine and TSH prior to initiation of treatment. Discuss with her what she will use for birth control and document this discussion.

Question 33

CASE 4…

Answer 33

27 yo male is admitted secondary to a manic episode. In reviewing his history you find he has 5 to 6 manic or depressive episodes a year. He has also struggled on and off with ETOH abuse. What medication would you like to start? Depakote would be a good choice because pt is a rapid cycler (4 or more depressive or manic episodes/year) and because of comorbid ETOH abuse. You start 250mg BD and titrate to 500mg BD. His depakote level is 70. You check his lfts and compared to baseline they have increased. It is not unusual for patients on anticonvulsants to experience an increase in lfts and as long as they do not more than triple no change in therapy is indicated. so keep monitoring.

Question 34

indications for use of antipsychotics

Answer 34

schizophrenia, schizoaffective disorder, bipolar disorder- for mood stabilization and/or when psychotic features are present, psychotic depression, augmenting agent in treatment resistant anxiety disorders

Question 35

What are the key pathways affected by Dopamine in the brain?

Answer 35

MESOCORTICAL (- dopamine), MESOLIMBIC (+), NIGROSTRIATAL (-), TUBEROINFUNDIBULAR (Blocking dopamine in this pathway will predispose your patient to hyperprolactinemia)

Question 36

what are Antipsychotic Typicals?

Answer 36

D2 dopamine receptor antagonists. Fluphenazine, Haloperidol, Pimozide, Risperidone

Question 37

what are Antipsychotic Atypicals?

Answer 37

serotonin-dopamine 2 antagonists (SDAs), They are considered atypical in the way they affect dopamine and serotonin neurotransmission in the four key dopamine pathways in the brain.

Question 38

what is the only drug proven to be benefitical in tx resistance? And explain its se’s

Answer 38

Clozapine. Is reserved for treatment resistant patients because of side effect profile but this stuff works!. Se: Agranulocytosis, seizures, abnormal lft’s, weight gain, increased levels of triglycerides

Question 39

what are adverse side effects of antipsychotics?

Answer 39

Tardive Dyskinesia (TD)-involuntary muscle movements, Neuroleptic Malignant Syndrome (NMS): Characterized by severe muscle rigidity, Extrapyramidal side effects (EPS): Acute dystonia, Parkinson syndrome, Akathisia.

Question 40

what agents cause EPS as a side effect?

Answer 40

Anticholinergics such as benztropine, trihexyphenidyl, diphenhydramine, Dopamine facilitators such as Amantadine, Beta-blockers such as propranolol

Question 41

CASE 5…

Answer 41

21 yo AA male with symptoms consistent with schizophrenia is admitted because of profound psychotic sx. He is treatment naïve. You plan to start an antipsychotic- what baseline blood work would you obtain? Fasting lipid profile, Fasting blood sugar, Lfts, CBC. start Risperidone. He starts to complain that he “feels uncomfortable in my skin like I can’t sit still”. What is likely going on and what are you going to do about it? Akathisia. This is not uncommon with Risperidone. treat akathisia as it is associated with suicide.

Question 42

what are Anxiolytics?

Answer 42

Used to treat many diagnoses including panic disorder, generalized Anxiety disorder, substance-related disorders and their withdrawal, insomnias and parasomnias. In combo with SSRI’s and SNRI’s for anxiety disorders

Question 43

name Anxiolytics…

Answer 43

Buspirone and Benzodiazapines (Used to treat insomnia, parasomnias and anxiety disorders. Often used for CNS depressant withdrawal protocols ex. ETOH withdrawal. Side effects/cons Somnolence, Cognitive deficits, Amnesia, Disinhibition, Tolerance, Dependence)

Question 44

whats another name for Alprazolam?

Answer 44

Xanax