Anxiolytics, antidepressants and antipsychotics

Question 1

what is the ICD 10 depression criteria?

Answer 1

Core symptoms: depressed mood, anhedonia, lack of energy

other symptoms: suicidal thoughts or plans, sleep disturbance, psychomotor agitation or retardation, low self esteem, changes in weight and appetite, poor concentration, guilt or self-reproach

Question 2

what is the ‘monoamine hypothesis of depression?’

Answer 2

decreased serotonin and/or noradrenaline levels causes mood disorders

• limitations: clinical effect of anti depressant drugs not seen until 2-3 weeks of continuous use

Question 3

what are some non-pharmacological treatments of depression?

Answer 3

cognitive behavioural therapy or interpersonal therapy

Question 4

How do selective serotonin reuptake inhibitors work?

Answer 4

they block pre-synaptic uptake of serotonin -

advantages: low toxicity in overdose, better tolerated at TCA, lack of addiction potential

Side effects: headaches, sexual dysfunction, movement disorders, risk of GI bleeding due to inhibition of 5-HT uptake into platelets especially when perscribed with aspirin

Question 5

what is a side effect of SSRIs that is especially prevalent in the elderly?

Answer 5

Hyponatraemia(especially elderly)

–Inappropriate secretion of anti diuretic hormone, consider in unexplained drowinessor confusion

Question 6

What is the MOA of Tricyclic anti-depressants?

Answer 6

it inhiibts noradrenaline and serotonin uptake - inhibits amine uptake at muscarinic, alpha-adenoreceptor and histamine

Question 7

what are the side effects of tricyclic anti-depressants?

Answer 7

poor tolerability and toxic in overdose (prolongation of QT interval)

Question 8

What is the MOA of monoamine oxidase inhibitors?

Answer 8

irreversible inhibitors of MOA- A and MOA- B -

only use in atypical depression/resistant versions

Question 9

what are the potential side effects of monoamine oxidase inhibitors?

Answer 9

potentiation of endogenous/exogenous sympathomimetic to give hypertensive crises

arrhythmias, headache and hypotension

Question 10

what drug is approved for use in social phobia disorders?

Answer 10

reversible mono-oxidase inhibitors

Question 11

how does Venlafaxine work?

Answer 11

inhibits pre-synaptic uptake of serotonin and noradrenaline

lack sedative and antimuscarinic effects of TCA

dose related hypertension and nausea

Question 12

How does Mirtazapine work?

Answer 12

pre-synaptic alpha2-adrenoreceptor antagonist, increases noradrenergic and serotonergic neurotransmission

Question 13

what is the MOA of Agomelatine?

Answer 13

it is a melatonin receptor agonist and selective serotonin receptor antagonist, favourable S/E profile

Question 14

how do the following brain regions contribute to anxiety?

Hippocampus

Hypothalamus

Brain Stem

Amygdala?

Answer 14

Hippocampus = interprets stimuli helping amygdala

amygdala = recieves stimuli as a threat - defense system

Hypothalamus = amygdala alerts hypothalamus for endocrine/autonomic response to fear

Brain Stem = contains the periaquaductual grey - which can initiate fear/fight/flight responses

Question 15

what neurotransmitters are implicated in anxiety?

Answer 15

noradrenaline -

• Abnormal noradrenergic activity, especially in the locus coeruleus, which has projections into the defense and behaviouralinhibition systems
• Drugsthat increase locus coeruleusfiring, e.g. stimulants, caffeine and yohimbineincreasethe release of noradrenaline (NA) and provoke anxiety.

GABA

• Suppress both the defense system and the behaviouralinhibition system, reducing anxiety.
• The amygdala is particularly sensitive to the GABA‑potentiating effects benxodiazepines(BDZ)

–The PAG seems to be less sensitive and this may explain why higher doses of BDZs are needed to treat panic states.

Serotonin

It modulates the activity of both the defense system and the behaviouralinhibition system

•The ‘Graeff‑Deakinhypothesis’suggests that serotonin is predominantlyanxiogenicin the limbic system and forebrain, while being anxiolytic in the PAG.

–Likely oversimplification as the pharmacological effects of anxiolytics, such as buspironeand the SSRIs are immediate, while their clinical anxiolytic actions are delayed.

Corticotrophin-releasing factor

•CRF is widely distributed in the brain with the highest concin hypothalamo‑pituitary axis (HPA).

–Autonomic, neuroendocrine and behaviouralresponses to stress initiated by the amygdala.

•Animal studies have shown it to have potent anxiogenicproperties

Cholecystokinin

Neuropeptide Y

Question 16

What is the treatment plan for anxiety?

Answer 16

1. SSRIs is recommended as first line treatment for 2 months
2. if no improvement with SSRIs after 2 months, increase dose or switch to alternative SSRI
3. If severe disabling anziety = short term Benzodiazepine like Lorazepam with regular review

Question 17

How do Benzodiazepines work as anxiety drugs?

Answer 17

enhances GABA mediated inhibition via increased frequency of Cl- Channel openings

Question 18

True or false

Anti-depressant therapy is appropriate in mild cases?

Answer 18

False - moderate/severe cases is most evident

Question 19

True or false:

TCA are more effect than SSRIs

Answer 19

false - they are equally effective

Question 20

True or false:

MAOI bind reversibly to MAO-A/MAO-B

Answer 20

False - irreversible

Question 21

True or false:

SSRIs have a lag phase of 2 weeks before therapeutic effect?

Answer 21

True

Question 22

True or false:

SSRIs are an effective treatment of acute anziety attacks?

Answer 22

false - there is a 2 week lag time - Benzodiazapenes for acute anxiety

Question 23

True or false:

benzodiapexines are appropriate for long term therapy

Answer 23

false - tolerance/addiction

Question 24

True or false:

Beta blockers are an effective treatement for the physical symptoms of anxiety?

Answer 24

True

Question 25

what is the lifetime risk of suicide in bipolar patients?

Answer 25

10-20%

Question 26

What is the first line of treatment for the manic phase of bipolar disorder?

Answer 26

1st line = anti-psychotics, lithium or Electroconvulsive therapy

Question 27

which antidepressants are more likely to be used in bipolar disorder?

Answer 27

SSRIs b/c they are less likey to induce a mania phase

Question 28

which drug is most evident at reducing suicide in bipolar disorder?

Answer 28

Lithium - though you must watch out for its narrow therapeutic index

Question 29

What is the MOA of Lithium?

Answer 29

Lithium is a monovalent cation that canmimic the role of sodium in excitable tissue, being able to permeate the voltage gated sodium channels that are responsible for action potential generation. It is not pumped out of the cell by sodium-potassium-ATPase and accumulates inside excitable cells, leading to a partial loss of intracellular potassium and depolarisation of the cell.

Question 30

what are some side effects of Lithium use?

Answer 30

renal tubular damage, thyroid disorders, hair loss, mild cognitive impairment, acne and weight gain

Question 31

what must we consider when perscribing Valproate?

Answer 31

teratogenicity especially in the first trimester

-30-40% of children exposed to Vlaproate in utero had developmental disorers

Question 32

•Michael 35 year old male, HxSchizophrenia, attends your general practice complaining of coughing, sneezing, lack of energy, nausea

–MedicationHx: clozapine, lactulose and hyoscinehydrobromide

• He informs you he has not eaten or taken his medication for 3 days
• What are you thinking?

Answer 32

–Missed dose of clozapine requires a re-dose titration due to risk of hypotension, seizures and cardiac arrthymias, may require change of monitoring frequency – contact relevant mental health team

–Infection = risk of agranulocytosis

Question 33

•A 58-year old patient was brought to the mental health clinic by his family. They said that for the past three weeks he had been hearing voices, dressing in a bizarre manner, and behaving strangely. They also mentioned that he was presently being treated for mild symptoms characteristic of early onset Parkinson’s disease. He was diagnosed with schizophrenia and was given quetiapine. What is the most likely reason for selecting this drug for this patient?

A.Itis an atypical AP which reduces the positive and negative symptoms of schizophrenia

B. It blocks D2 and 5-HT2 receptors and is less likely to exacerbate the underlying Parkinson’s while decreasing the positive symptoms.

C. It is more effective at reducing positive symptoms

D. It may treat both the parkinsonsdisease and schizophrenia symptoms

Question 34

•A 33 year old female was brought to hospital for acute mental status change by her husband. On examination the woman is some rigidity of her extremities. Her blood pressure is 198/109, Temperature 39°C. Blood analyses show grossly elevated creatinekinase. Which of the following medications most likely to cause her serious condition?

•A.Levodopa
B. Dantrolene
C. Fluoxetine
D. Morphine
E. Chloropromazine