Psychopharmacology in Psychiatry Flashcards
What is Indication?
Indication: Establish a diagnosis and identify
the target symptoms that will be used to
monitor therapy response.
Why is “choice of agent and dosage” important?
Choice of agent and dosage: Select an
agent with an acceptable side effect profile
and use the lowest effective dose.
Remember the delayed response for many
psych meds and drug-drug interactions.
What is management of medications?
Management: Adjust dosage for optimum
benefit, safety and compliance. Use
adjunctive and combination therapies if
needed however, always strive for the
simplest regime.
*If initial treatment isn’t successful. Keep as simple as possible
What is 2 general guidelines when prescribing Antidepressants?
Antidepressant efficacy is similar!! (Similar side effects) - All work at about a 70% response rate
Selection is based on past history of a response, side effect profile and coexisting medical conditions.
How long do anti-depressants take to work and how long should we wait before swapping them?
There is a delay typically of 2-4 weeks after a
therapeutic dose is achieved before symptoms improve. (Delayed response to do with amygdala receptor changes).
If no improvement is seen after a trial of
adequate length (at least 2 months) and
adequate dose, either switch to another
antidepressant or augment with another agent.
What conditions would we prescribe Anti-depressants for?
- Unipolar and bipolar depression
- Organic mood disorders
- Schizoaffective disorder
- Anxiety disorders including OCD, panic, social phobia, PTSD,
Premenstrual dysphoric disorder and impulsivity associated with personality disorders. (Evidence is mixed for this)
What are the different classifications of Antidepressants?
- Selective Serotonin Reuptake Inhibitors (SSRIs)
- Tricyclics (TCAs)
- Monoamine Oxidase Inhibitors (MAOIs)
- Serotonin/Noradrenaline Reuptake Inhibitors (SNRls)
- Novel antidepressants (work slightly differently)
How do SSRI’s work?
By blocking the presynaptic serotonin reuptake
What are SSRI’s used to treat?
Anxiety and depressive symptoms
What are the most common side effects of SSRI’s ?
Most common side effects include Gl upset,
sexual dysfunction (30%+!), anxiety,
restlessness, nervousness, insomnia, fatigue or sedation, dizziness
Very little risk of cardiotoxicity in overdose
Can develop a discontinuation syndrome with
agitation, nausea, disequilibrium and dysphoria
What is activation syndrome seen in SSRI use?
Cause increased serotonin. It can be distressing for the patient.
Nausea, increased anxiety, panic and
agitation.
Typically last 2 — 10 days (Warn patients!)
*If had activation syndrome in past could give short course benzos when starting
What is Discontinuation syndrome?
Agitation, nausea, disequilibrium and dysphoria
More common with shorter half life drugs
so conisder switching to fluoxetine.
Takes about 3 weeks to get out of system
What are the Pros and Cons of Fluoxetine (Prozac)?
Fluoxetine (Prozac) Pros;
- Long half-life so decreased incidence of discontinuation
syndromes. Good for pts with medication noncompliance issues
- Initially activating so may provide increased energy
- Secondary to long half-life, can give one 20m tab to taper someone off SSRI when trying to prevent SSRI Discontinuation Syndrome
Fluoxetine (Prozac) Cons;
- 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 patients already on a number of meds
- Initial activation may increase anxiety and insomnia
- More likely to induce mania than some of the other SSRls
What are the Pros and Cons of Sertraline?
Sertraline Pros;
- Very weak P450 interactions (only slight CYP2D6)
- Short half-life with lower build-up of metabolites
- Less sedating when compared to paroxetine
Sertraline Cons;
- Max absorption requires a full stomach
- Increased number of Gl adverse drug reactions
What are the Pros and Concs of Tricyclic Antidepressants (TCA’s) in general?
Very effective but potentially unacceptable
side effect profile i.e. antihistaminic, anticholinergic, antiadrenergic
Lethal in overdose (even a one week supply can be lethal!)
Can cause QT lengthening even at a therapeutic serum level
What are Tertiary TCA’s and how do they work?
- Have tertiary amine side chains
- Side chains are prone to cross-react with other types of receptors, which leads to more side effects
- Examples: lmipramine, amitriptyline, doxepin, clomipramine
- Have active metabolites including desipramine and nortriptyline
(A metabolite is any substance produced during metabolism (digestion or other bodily chemical processes)).
What are Secondary TCA’s and how do they work?
- Are often metabolites of tertiary amines
- Primarily block noradrenaline
- Side effects are the same as tertiary TCAs but generally are less severe
- Examples: Desipramine, notrtriptyline
(A metabolite is any substance produced during metabolism (digestion or other bodily chemical processes)).
What are Monoamine Oxidase Inhibitors (MAOI’s) and how do they work?
- Bind irreversibly to monoamine oxidase thereby preventing inactivation of amines such as norepinephrine, dopamine and serotonin leading to increased synaptic levels.
- Are very effective for resistant depression
- Side effects include orthostatic hypotension, weight gain, dry mouth, sedation, sexual dysfunction and sleep disturbance
- Hypertensive crisis can develop when
MAOI’ s are taken with tyramine-rich foods
or sympathomimetics. Cheese Reaction!! (Prevent breakdown of tyramine - increase BP, increase side effects. Foods like Cheese, red wine, some beans, some processed meats) - Not used very often
How can Serotonin Syndrome occur in MAOI’s and what should you do as a caution?
Serotonin Syndrome can develop if 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. The exception of fluoxetine where need to wait 5 weeks because of long half-life.
How do SNRI’s work?
Serotonin/Norepinephrine reuptake inhibitors (SNRls);
- 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 (at low doses 10% of dose)
Examples;
- Venlafaxine
- Duloxetine
- Vortioxetine
What drug is most commonly used for Neuropathic pain?
Amitriptyline (A SNRI) at low doses 10% of normal dose
What are the Pros and Cons for Venlafaxine?
Venlafaxine Pros;
- Minimal drug interactions and almost no P450 activity
- Short half life and fast renal clearance avoids build-up (good for geriatric populations)
Venlafaxine Cons;
- Can cause a 10-15 mmHG dose dependent increase in diastolic
- May cause significant nausea, primarily with immediate-release (IR) tabs
- Can cause a bad discontinuation syndrome, and taper recommended after 2 weeks of administration
- Sexual side effects in >30%
What are the Pros and Cons for Duloxetine?
Duloxetine Pros;
- Some data to suggest efficacy for the physical symptoms of depression
- Thus far less BP increase as compared to
venlafaxine, however this may change in time
Duloxetine Cons;
- CYP2D6 and CYPIA2 inhibitor
- Cannot break capsule, as active ingredient not stable within the stomach
- In pooled analysis had higher drop out rate
What are the Pros and Cons of Vortioxetine?
Vortioxetine SNRI Pros;
- Less Gl side effects
- Less change in blood pressure
Cons;
- Expensive (GP’s cannot prescribe, SNRI expensive, less side effects - specialist only)
What is the one Novel Antidepressant and its Pros and Cons?
Mirtazapine Pros;
- Different mechanisms of action may provide a good augmentation strategy for SSRls. Is a 5HT2 and 5HT3 receptor antagonist
- Can be utilised as a hypnotic at lower doses secondary to antihistaminic effects
Mirtazapine Cons;
- Increases serum cholesterol by 20% in 15% of patients and triglycerides in 6% of patients
- Very sedating at lower doses. At doses of 30mg and above, it can become activating and require a change of administration time to the morning.
- Associated with weight gain (particularly at doses below 45mg)
(Reserved for resistance cases or in the elderly)
Susie has a depressive episode with no history
of hypomania or mania. She has depressed
mood, not eating, psychomotor retardation and poor sleep with early morning wakening.
What agent would you like to use for her?
Establish dx: Major depressive disorder
Target symptoms: depression, poor appetite,
psychomotor retardation and insomnia
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.
Less desirable choices include Paroxetine
and Mirtazapine because of sedation and
wt gain.
Not a duel reuptake inhibitors because she
is treatment naive. (SNRI)
Not a TCA because of side effects
Bob is a 55 year old diabetic man with mild
hypertnesion 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 mirtazepine. His depression was improved slightly with each of these meds but never remitted. What would you like to treat him with?
Establish dx: Major depressive disorder with
anxious features
Target symptoms: depressive sx, anxiety and
possibly his neuropathic pain
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 HT 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!!
What medications can we use for Treatment Resistant Depression?
- Combination of antidepressants, eg SSRI
or SNRI with Mirtazepine - Adjunctive treatment with Lithium (Mood stabiliser)
- Adjunctive treatment with atypical
antipsychotic eg Quetipaine, Olanzapine
or Aripiprazole (1 in 5 chance of treating depression) - ECT!!
What is Electroconvulsive Therapy (ECT) and its side affects?
Electroconvulsive Treatment therapy. Have anaesthetic (propofol) and muscle relaxant. Pass electricity through brain to stimulate epileptic seizure between 20-60 secs twice a week for 3.5 weeks has an 80% response rate for depression and takes about 20 mins.
Side effects - anaesthetic risk, reduces firing in dorsal frontal pre-cortex (can also cause short term memory loss). Contraindications - intracranial hypertension and cardiac clotting diseases
What are the medications for Treatment Resistant Anxiety?
- High dose SSRI first (Sometimes above max dose)
- Combination of antidepressants eg SSRI
or SNRI with Mirtazepine - Adjunctive treatment with atypical
antipsychotic eg Quetiapine, Olanzapine or Risperidone - Adjunctive treatment with Pregabalin or
buspirone - Diazepam does not treat underlying
cause!! Avoid as body develops tolerance
Why is patient Prophylaxis important?
Prophylaxis - Taking medication to make sure no recurrence of disease
- First episode continue for 6mth to a year
- Second episode continue for 2 years
- Third episode disucuss life long
American studies suggested if :
- Stop before 6 months 80% relapse
- Prophylaxis > 6 months 20% relapse
(Important to take meds)
What are the indications of Mood Stabilisers ?
- Bipolar
- Cyclothymia
- Schizoaffective
What medications are approved for used in Bipolar Disorder?
- Aripiprazole
- Olanzapine
- Quetiapine
- Riperdone
- Quetiapine XR
