Pharm - GAD, OCD, Insomnia Flashcards
What are the first line agents for the tx of GAD?
Antidepressants: SSRI and SNRI
Which psychic symptoms in patients with GAD that are best treated with SSRI and SNRI?
Apprehension and worry
Which antidepressants are preferred when a patient has GAD and depression?
- antidepressants are preferred over benzodiazepines
- antidepressants are effective treatments for both conditions (GAD and depression)
What is the time to onset of clinical effect when using antidepressants for GAD?
- for an SRI, it varies by patient but averages approximately 4 weeks.
- the initial therapeutic dose should be continued for 4-6 weeks.
What are the 2 meds used to augment the effects of antidepressants in the tx of GAD?
Anxiolytic: buspirone (Buspar®)
Anticonvulsant: pregabalin (Lyrica®, Schedule V) Not FDA approved for GAD
What is the time to onset of clinical effect when using buspirone or pregabalin in the treatment of GAD?
Buspirone should be given a trial of 4-6 weeks at the maximally tolerated dose before concluding it is ineffective.
Pregabalin minimum of 4-6 weeks at a maximally tolerated dose before concluding that it is not effective.
What is the drug of choice for rapid relief of acute anxiety sx?
Benzodiazepines are the drug of choice for rapid relief of ACUTE anxiety symptoms
What is the role of a benzodiazepine in the treatment of GAD when initiating an antidepressant?
- can be used as either monotherapy or, more commonly, as an adjunct to antidepressant treatment
- commonly used in GAD for acute management of anxiety and worry during the period before SSRIs or SNRIs take effect
- counteract the initial agitation often caused by the SSRI
- once the patient responds to the SSRI, the benzodiazepine can be tapered off gradually.
Which somatic symptoms in pts with GAD are best treated with benzodiazepines?
- restlessness
- increased fatiguability
- difficulty in concentrating
- irritability
- muscle tension
- sleep disturbance
Which autonomic symptoms in pts with GAD are best treated with benzodiazepines?
- shortness of breath
- palpitations,
- sweating
- dry mouth
- dizziness
- abdominal distress
- they generally lead to a reduction of emotional and somatic symptoms within minutes to hours, depending on the specific medication
Which patients are good candidates for long-term, low-dose benzodiazepines in the tx of GAD?
- patients with chronic GAD
- who have minimal current depressive symptoms
- who have no history of a substance use disorder
- do not develop tolerance to their anxiolytic effects, which would require dose increase
- experience only mild, tolerable withdrawal symptoms when the medication is tapered off
Which patients are poor candidates for long-term, low-dose benzodiazepines in the tx of GAD?
- h/o a substance abuse disorder
- patients who develop rapid tolerance
- increase their doses against medical advice
- exhibit withdrawal symptoms between doses
MOA of benzodiazepines (BZD)
Benzodiazepines exert their principal pharmacodynamic effect via central nervous system GABA receptors, potentiating the effects of endogenous GABA, the main inhibitory neurotransmitter.
**GABA receptors are membrane-bound proteins that primarily mediate neuronal excitability (seizures), rapid mood changes, clinical anxiety, sleep, memory, mood, and analgesia.
Which benzos are more likely to exert acute withdrawal symptoms?
Benzodiazepines with shorter elimination half-lives:
- alprazolam (Xanax)
- lorazepam (Ativan)
- etc.
Which benzos are less likely to exert acute withdrawal symptoms?
Benzodiazepines with longer elimination half-lives
- diazepam (Valium)
- clonazepam (Klonopin)
Describe the psychomotor retardation caused by benzodiazepines
- drowsiness, poor concentration, mental confusion
- ataxia, motor coordination, muscle weakness
- diplopia, vertigo
- slow reaction time and impaired driving skills increasing the risk of motor vehicle crashes
Describe memory impairment caused by BZD
Anterograde amnesia: impaired episodic memory – remembering recent events, circumstances under which they occurred and the time sequence
In patients who have used more than one year – specific deficits in visual-spatial ability and sustained attention.
Contraindications to BZD
Adverse effects in PREGNANCY:
- class D teratogen
- can cross the placenta and cause development of dependence and withdrawal in the fetus
- excreted in breast milk: contraindicated in breast-feeding mothers
Describe physiologic and psychologic dependence cause by BZD.
- develops sooner (1-2 months) in patients taking high dose of high-potency agents (example is alprazolam)
- withdrawal symptoms emerge with rapid dose reduction or abrupt discontinuation of the drug
- psychologic: overreliance on the need for the drug, loss of self-confidence and varying degrees of drug-seeking behavior
What is the primary cause of withdrawal symptoms in a patient taking a BZD?
any abrupt or overly rapid reduction in benzodiazepine (BZD)
Given a patient who abruptly stops a BZD, identify the withdrawal symptoms.
S/sx can include tremors, anxiety, perceptual disturbances, dysphoria, psychosis, and seizures.
What is the relationship between the half-life of BZD and withdrawal symptoms?
- the onset of withdrawal varies according to the half-life of the BZD involved
- sx may be delayed up to three weeks in BZDs with long half-lives, but may appear as early as 24 to 48 hours after cessation of BZDs with short half-lives.
Describe the the appropriate, safe withdrawal plan for benzodiazepine withdrawal from a patient.
- individualize the taper
- taper BZD slowly and gradually
One approach:
- 10-25% reduction of the initial dose every one to two weeks until the lowest dose is reached
- monitor the patient for symptoms of benzodiazepine withdrawal or relapse of GAD and slow the rate of dose reduction accordingly
- early signs of withdrawal include anxiety, dysphoria, and tremor; advanced manifestations include perceptual disturbances, psychosis, and seizures.
- if a patient has failed a previous tapering regimen, then try a slower taper over 6 months.
- augment taper with cognitive-behavioral therapy to improve the likelihood of success.
What is the place in therapy for mirtazapine?
Mirtazapine (Remeron) is a sedating antidepressant
-can be used as monotherapy or adjunctive treatment for GAD
What is the place in therapy for hydroxyzine?
Hydroxyzine (Vistaril) is an antihistamine
- it’s more sedating than BZDs and buspirone, and thus potentially useful for treating insomnia associated with GAD
- can also be used as monotherapy in non-depressed patients who received no benefit from the SRIs and/or tolerated them poorly
What is the place in therapy for quetiapine?
Quetiapine (Seroquel) is a SGA
- can be used in the tx of resistant GAD
- use these drugs in GAD only after safer alternatives have been exhausted
- use adjunctively, augmenting an antidepressant or as monotherapy in patients who have had little to no response to prior drug trials
What is the duration of the therapy for drug treatment of GAD?
if effective, antidepressant treatment for generalized anxiety disorder (GAD) should be continued for at least 12 months.
What is the drug class of choice for the treatment of panic attacks?
SSRI are the first line agents because of their tolerability and efficacy in acute and long-term studies.
BZD are the most commonly used drugs for panic disorder BUT, are considered second-line drugs because of the risk of dependency.
What are the BZD preferred agents for the treatment of panic attacks?
- alprazolam (Xanax)
- clonazepam (Klonopin)
Duration of therapy for the tx of panic attacks?
total of therapy 12 months before drug discontinuation is attempted
What are the drugs of choice for the treatment of obsessive-compulsive disorders?
-cognitive-behavioral therapy (CBT) and serotonin reuptake inhibitors (SSRIs).
**SSRI: fluoxetine, paroxetine, sertraline, citalopram and escitalopram
**Tricyclic antidepressant (“old” SNRIs): clomipramine (Anafranil) inhibits the reuptake of serotonin and norepinephrine
If a pt with OCD with has an inadequate response to first line agents, what are the alternative therapies?
- providing combined treatment (SRI and CBT)
- augmenting an SRI with an antipsychotic medication
- switching to a different SRI
- switching to venlafaxine
List the benzodiazepines to treat insomnia
triazolam (Halcion®) lorazepam (Ativan®) estazolam (Prosom®) temazepam (Restoril®) flurazepam (Dalmane®) quazepam (Doral®)
List the nonbenzodiazepines hypnotics to treat insomnia
zaleplon (Sonata®)
zolpidem (Ambien®)
eszopiclone (Lunesta®)
What is the orexin receptor antagonist to treat insomnia?
suvorexant (Belsomra®)
What is the melatonin receptor agonist to treat insomnia?
ramelteon (Rozerem®)
What is the TCA antidepressant to treat insomnia?
doxepin (generic)
What products can be used to induce sleep in a patient with sleep onset insomnia?
- short-acting medication is a reasonable choice for an initial trial of pharmacologic therapy.
- this may improve the insomnia with less residual somnolence the following morning.
Examples of short-acting medications (duration of effect ≤8 hours) include:
- zaleplon (Sonata)
- zolpidem (Ambien)
- triazolam (Halcion)
- ramelteon (Rozerem)
What products can be used to help maintain sleep in a patient with sleep maintenance insomnia?
-longer-acting medication is preferable for an initial trial of pharmacologic therapy.
Examples of longer-acting medications include:
- zolpidem (Ambien) extended release
- eszopiclone (Lunesta)
- temazepam (Restoril)
- flurazepam (Dalmane)
- estazolam (Prosom)
- low dose doxepin
- suvorexant (Belsomra)
*These medications may increase the risk for hangover sedation and patients must be warned about this possibility.
If a patient awakens in the middle of night with insomnia, what is the medication and the dosage form used to help induce sleep?
zaleplon (Sonata) and a specific sublingual tablet form of zolpidem (Ambien)
What must patients with middle of the night insomnia be warned of?
there must be at least 4 hours of time in bed remaining after administration
What other issues must be considered when prescribing an insomnia medication?
- cost
- adverse effects
- physical and psychological addiction with long term use
- concurrent conditions/diseases
- pregnancy
- alcohol consumption
- renal or hepatic disease
- pulmonary disease or sleep apnea
- nighttime decision making
- older adults
What ADR are common to all agents used to treat insomnia?
- adverse effects associated with the nonbenzodiazepines are similar to those associated with benzodiazepines.
- frequency and severity of nonBZD may be less as compared to BZD (possibly related to their shorter 1/2 life).
- next morning impairment has been increasingly recognized with higher doses.
Other ADR reported in nonBZD
- unpleasant taste (eszopiclone, Lunesta) and hallucinations (zolpidem, Ambien)
- the incidence of infection (e.g., upper respiratory, otitis media, urinary tract, conjunctivitis, others) may also be increased among patients taking a nonbenzodiazepine
What kind of insomnia can BZD and non-BZD cause with long-term use?
Rebound insomnia
What sleep-related behaviors are associated with meds used to treat insomnia?
- sleep-related behaviors (e.g., sleep walking, driving, making telephone calls, eating, or having sex while not fully awake)
- anterograde amnesia (particularly with triazolam (Halcion) or when used with alcohol)
- aggressive behavior
- severe allergic reaction
What is the major drug interaction with suvorexant (Belsomra)
- CYP3A4 inhibitors
- Suvorexant has a 12-hour half-life
- There is potential for increased toxicity when used in combination with CYP3A4 inhibitors
How should patients be recommended to take suvorexant (Belsomra)?
5 mg in patients taking moderate CYP3A4 inhibitors (examples: amiodarone, diltiazem, grapefruit juice)
**It is not recommended for use in combination with strong CYP3A4 inhibitors (clarithromycin, ketoconazole)
Effects of insomnia drugs on the elderly
high risk of adverse effects from hypnotic drugs including:
- excessive sedation
- cognitive impairment
- delirium
- night wandering
- agitation
- postoperative confusion
- balance problems
- impaired performance of daily activities
- increased risk of falls
