Pharmacological Treatments of Affective and Anxiety Disorders Flashcards
what are the indications for antidepressants?
Indications: 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.
how do antidepressants work?
how do you select which antidepressant to use?
Antidepressant efficacy is similar so selection is based on past history of a response, side effect profile and coexisting medical conditions.
how long does it take for antidepressants to show an effect and what do you do if it doesnt show an effect?
There is a delay typically of 2-4 weeks after a therapeutic dose is achieved before symptoms improve.
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 are the different antidepressant classifications?
Tricyclics (TCAs)
Monoamine Oxidase Inhibitors (MAOIs)
Selective Serotonin Reuptake Inhibitors (SSRIs)
Serotonin/Noradrenaline Reuptake Inhibitors (SNRIs)
Novel antidepressants
what are the features TCAs and what can it cause?
Very effective but potentially unacceptable side effect profile i.e. antihistaminic (weight gain, sleepy), anticholinergic, antiadrenergic (dry mouth, blurred vision)
Lethal in overdose (even a one week supply can be lethal!)
Can cause QT lengthening even at a therapeutic serum level
how do TCAs work?
work by increasing both serotonin, dopamine and noradrenaline
what are the 2 types of TCAs?
Tertiary TCAs - Have tertiary amine side chains, Side chains are prone to cross react with other types of receptors which leads to more side effects
Secondary TCAs - Are often metabolites of tertiary amines, Primarily block noradrenaline, Side effects are the same as tertiary TCAs but generally are less severe
what are Monoamine Oxidase Inhibitors (MAOIs)?
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
what is the cheese reaction?
Hypertensive crisis can develop when MAOI’s are taken with tyramine-rich foods or sympathomimetics. *Cheese Reaction!!
Cheese
Red wine
Some processed meats
Strict diet
what is serotonin syndrome and what does it cause?
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 Selective Serotonin Reuptake Inhibitors (SSRIs)?
Block the presynaptic serotonin reuptake (so increase levels)
Treat both anxiety and depressive sx
what are the side effects of SSRIs?
Most common side effects include GI 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 (when you stop them quickly)
Discontinuation syndrome is more common with what drugs?
More common with shorter half life drugs so consider switching to fluoxetine (as longer half life).
whata re the symptoms of activation syndrome?
Activation Syndrome: Cause increased serotonin. Cab be distressing for patient
Nausea, increased anxiety, panic and agitation
whata re the pros and cons of Sertraline (SSRI)?
Pros”
- Very weak P450 interactions (only slight CYP2D6)
- Short half life with lower build-up of metabolites
- Less sedating when compared to paroxetine
Cons:
- Max absorption requires a full stomach
- Increased number of GI adverse drug reactions
what are the pros of Fluoxetine (Prozac) - SSRI?
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 20mg tab to taper someone off SSRI when trying to prevent SSRI Discontinuation Syndrome
what are the cons of Fluoxetine (Prozac) - SSRI?
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
Initial activation may increase anxiety and insomnia
More likely to induce mania than some of the other SSRIs
what are Serotonin/Norepinephrine reuptake inhibitors (SNRIs), how do they work and what are the used for?
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
Go-to med if someone hasn’t response to SSRI
what are the pros and cons of Venlafaxine (SNRI)?
Pros:
- Minimal drug interactions and almost no P450 activity
- Short half life and fast renal clearance avoids build-up (good for geriatric populations)
Cons:
- Can cause a 10-15 mmHG dose dependent increase in diastolic BP
- May cause significant nausea, primarily with immediate-release (IR) tabs
- Can cause a bad discontinuation syndrome, and taper recommended after 2 weeks of administration
- Noted to cause QT prolongation
- Sexual side effects in >30%
what are the pros and cons of Duloxetine (SNRI)?
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
Cons:
- CYP2D6 and CYP1A2 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 Novel antidepressants
Mirtazapine?
Pros:
- Different mechanism of action may provide a good augmentation strategy to SSRIs (Effects different serotonin receptors to SSRIs). Is a 5HT2 and 5HT3 receptor antagonist
- Can be utilized as a hypnotic at lower doses secondary to antihistaminic effects
Cons:
- Increases serum cholesterol by 20% in 15% of patients and triglycerides in 6% of patients
- Very sedating at lower doses. At doses 30mg and above it can become activating and require change of administration time to the morning
- Associated with weight gain (particularly at doses below 45mg)
Case 1:
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
Target symptoms: depression, hyperphagia, psychomotor retardation and hypersomnolence
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 naïve
Not a TCA because of side effects
Case 2:
ob is a 55 year old diabetic man with mild HTN (hypertension) 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
SNRI = dual
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!!
