Psychopharmacological Treatment of Psychotic Disorders II - Antipsychotic and Benzodiazpeine

Question 1

what are antipsychotics?

Answer 1

Antipsychotics, also known as neuroleptics, are a class of medication primarily used to manage psychosis, principally in schizophrenia but also in a range of other psychotic disorders. They are also the mainstay together with mood stabilizers in the treatment of bipolar disorder

Question 2

what are the indicaitons for antipsychotics?

Answer 2

Indications for use: 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 3

what is the key pathway in the brain that antipsychotics affect?

Answer 3

Antipsychotic affect dopamine

Reduce amount of dopamine in pathways in brain

MESOCORTICAL- where the negative symptoms and cognitive disorders (lack of executive function) arise. Problem here is too little dopamine

MESOLIMBIC - where the positive symptoms come from (hallucinations, delusions, and thought disorders). Problem too much dopamine

NIGROSTRIATAL- involved in movement regulation. dopamine suppresses acetylcholine activity. Dopamine hypoactivity can cause Parkinsonian movements i.e. rigidity, bradykinesia, tremors), akathisia (restless legs) and dystonia

TUBEROINFUNDIBULAR - dopamine release inhibits/regulates prolactin release. Blocking dopamine in this pathway will predispose your patient to hyperprolactinemia (gynecomastia/galactorrhea/decreased libido/menstrual dysfunction)

Question 4

what are Antipsychotics: Typicals?

Answer 4

Are D2 dopamine receptor antagonists

Examples include Fluphenazine, Haloperidol, Pimozide

Question 5

what are the risks of typical antipsychotics?

Answer 5

High potency typical antipsychotics bind to the D2 receptor with high affinity. As a result they have higher risk of extrapyramidal side effects (pariksonian)

Question 6

Low potency typical antipsychotics have ____ affinity for the D2 receptors but tend to interact with nondopaminergic receptors resulting in more ______ and anticholinergic adverse effects including sedation, hypotension

Examples include chlorpromazine and Thioridazine

Answer 6

less

cardiotoxic

Question 7

what are atypical antipsychotics?

Answer 7

atypical agents are 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

Typical antipsychotic drugs act on the dopaminergic system, blocking the dopamine type 2 (D2) receptors. Atypical antipsychotics have lower affinity and occupancy for the dopaminergic receptors, and a high degree of occupancy of the serotoninergic receptors 5-HT2A

Question 8

what are examples of atypical antipsychotics?

more info on the powerpoint of these form slides 71 to 74

Answer 8

Risperidone (Risperdal) - Increased extrapyramidal side effects, weight gain and sedation, hyperprolactinemia

Olanzapine (Zyprexa) - weight gain, may cause hypertriglyceridemia, hypercholesterolemia, hyperglycemia

Quetiapine (Seroquel) - may cause abnormal LFTs, orthostatic hypotension

Aripiprazole (Abilify) - Unique mechanism of action as a D2 partial agonist (means lower incidence of extrapyramidal side effects, much less sedation and no typical heart problems), no weight gain

Question 9

what is Clozapine (Clozaril)?

Answer 9

atypical antipsychotic

reserved for treatment resistant patients because of side effect profile but this stuff works!

Increased risk of seizures (especially if lithium is also on board)

Associated with the most sedation, weight gain and abnormal LFT’s

If someone becomes treatment resistant and they have had a trial of 1 antipsychotic for 8 weeks and a second for the same time and a treatment dose then our go to medication would be clozapine

Need to have regular blood test

Question 10

what are Antipsychotic adverse effects?

Answer 10

Tardive Dyskinesia (TD)-involuntary muscle movements that may not resolve with drug discontinuation- risk approx. 5% per year

Neuroleptic Malignant Syndrome (NMS): Characterized by severe muscle rigidity, fever, altered mental status, autonomic instability, elevated WBC, CPK and lfts. Potentially fatal

Extrapyramidal side effects (EPS): Acute dystonia, Parkinson syndrome, Akathisia

Question 11

what are Agents for EPS?

Answer 11

Anticholinergics such as benztropine, trihexyphenidyl, diphenhydramine

Dopamine facilitators such as Amantadine

Beta-blockers such as propranolol

Need to watch for anticholinergic SE particularly if taken with other meds with anticholinergic activity ie TCAs

Question 12

Commonest psychotic symptom is lack of _______

People with psychotic illnesses relapse most commonly due to non _________

Only 30% of patients take medication as prescribed

After third episode of schizophrenia clear link to reduced ________, lower IQ and negative ________

Consider ____ Acting Intramuscular!!

Answer 12

insight

compliance

functioning

symptoms

Long

Question 13

Case:

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?

Answer 13

Many atypical antipsychotics can cause dyslipidemia, abnormal LFT’s and elevated blood sugars and there is a class risk of diabetes unrelated to weight gain so you need the following:

Fasting lipid profile

Fasting blood sugar

Lfts

CBC

Question 14

case continued:

His labs come back as follows:

Total Cholesterol:215 (raised) HDL:30 LDL:145

Glucose 88 (slightly raised)

Lfts, CBC Normal

What agent would you like to start?

Answer 14

Pt has mildly elevated total cholesterol and a low HDL for his age. Would not choose Olanzapine or Quetiapine given risk of dyslipidemia. Risperidone, (Ziprasidone) or Aripiprazole are good choices. (as both weight neutral)

Question 15

case continued:

You start Risperidone and titrate to 3mg BID (high average dose). 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?

Answer 15

He is likely experiencing akathisia. This is not uncommon with Risperidone. Given he was very ill reducing the dose may not be the best choice so likely treat with an anticholinergic agent or propranolol. You need to treat akathisia because it is associated with an increase risk for suicide!

Question 16

what are Anxiolytics used for?

Answer 16

Used to treat many diagnoses including panic disorder, generalized Anxiety disorder, substance-related disorders and their withdrawal, insomnias and parasomnias. In anxiety disorders often use anxiolytics in combination with SSRIS or SNRIs for treatment

Question 17

Buspirone (Buspar) is a Anxiolytics, what is its pros and cons?

Answer 17

Pros:

Good augmentation strategy- Mechanism of action is 5HT1A agonist. It works independent of endogenous release of serotonin

No sedation

Cons:

Takes around 2 weeks before patients notice results

Will not reduce anxiety in patients that are used to taking BZDs because there is no sedation effect to “take the edge off

Question 18

what are Benzodiazapines used for?

Answer 18

Used to treat insomnia, parasomnias and anxiety disorders

Often used for CNS depressant withdrawal protocols ex. ETOH withdrawal

Benzodiazepines act as a sedative – slowing down the body’s functions – and are used for both sleeping problems and anxiety. They work by increasing the effect of a brain chemical called GABA

Question 19

what are the side effects of benzodiazapines?

Answer 19

Somnolence

Cognitive deficits

Amnesia

Disinhibition

Tolerance

Dependence