What Works For Anxiety Disorders-Anti-Anxiety Drugs

Antianxiety Drugs

 Benzodiazepines (BD) – the most effective antianxiety drugs

Antidepressants

–Selective serotonin reuptake inhibitors (SSRIs)

–Tricyclic antidepressants (TCAs)

–Heterocyclics

• Mixed norepinephrine/serotonin reuptake inhibitors
• Mixed-action drugs

–Monoamine oxidase inhibitors (MAOIs)

• Buspirone
• Antipsychotics (neuroleptics)
• Barbiturates
• Antihistamines
• Clonidine
• Beta-blockers
• Meprobamate and derivatives
• Antiepileptic drugs
• Alcohol

Benzodiazepines (BD)

Mechanism of action:

• Facilitate neuronal membrane inhibition by actions as specific receptors

• Binds to specific receptors in CNS that are involved in modulation of GABA (γ-aminobutyric acid) transmission (enhancement of affinity of GABA)

• This inhibitory neurotransmitter increses the influx of chloride ions through cell membrane channels, thus inhibiting membrane depolarization
• BD do not substitute for GABA but appear to enhance GABA’s effects without directly activating GABA receptors or opening the associated chloride channels

• The enhancement in chloride ion conductance induced by the interaction of BD with GABA takes the form of an increase in the frequency of chanel-opening events

• Receptors for BD – in many brain regions (thalamus, limbic structures, cerebral cortex)

Short-acting BD: •Midazolam  •Lorazepam  •Oxazepam  •Alprazolam  •Halazepam

Long-acting BD: •Diazepam  •Chlordiazepoxide  •Chlorazepate  •Prazepam  •Clonazepam

Administration

• They are best used only for brief periods (psychological and physiological dependence, tolerance)

• The best results – treating time-limited anxiety (in response to clear-cut stress and when treatment lasts less than 8 weeks)
• Chronic anxiety, limited intrapsychic or external resources, inefficacy of buspirone and antidepressants – may need long-term therapy
• Repeated treatment – often necessary

Addiction

• Is rare in medical patients
• Individuals with a history of alcohol or drug abuse, physician shopping, antisocial behavior – are at risk of abusing BD
• The most frequently abused BD: •diazepam •alprazolam •lorazepam

Adverse effects

– sedation, impaired cognitive defects (difficulty focusing attention, memory impairment, confusion), disinhibition, tolerance, abuse potential, withdrawal, may cause or aggravate depression

Abstinence syndromes (withdrawal symptoms)

• May appear up to 10 days after abrupt discontinuation of moderate doses of BD that have been taken for more than 1 month
• Anxiety, insomnia, irritability, at times psychosis, delirium, seizures
• Some patients – withdrawal symptoms lasting up to 1 year
• Withdrawal is more abrupt and severe after discontinuation of short-acting BD•

SSRIs

:  Fluoxetine  •Sertraline  •Paroxetine  •Fluvoxamine  •Citalopram  •Escitalopram

Side effects:  headache, nausea and other gi effects, jitteriness, insomnia, sexual dysfunction, can affect plasma levels of other meds, akathisia rare

TCAs

: Amitryptyline, Nortriptyline, Imipramine, Desipramine, Doxepin, Clomipramine

Side effects: anticholinergic (dry mouth, tachycardia, constipation, urinary retention, blurred vision), sweating, tremor, postural hypotension, cardiac conduction delay, sedation, weight gain

Mixed norepinephrine/serotonin reuptake inhibitors •Venlafaxine •Mirtazapine

Side effects: nausea, dizziness, dry mouth, headaches, increased blood pressure, anxiety and insomnia, somnolence, weight gain, neutropenia rare

Mixed-action drugs:  •Bupropion  •Trazodone  •Nefazodone  •Amxapine

Side effects:

jitteriness, flushing, seizures in at-risk patients, anorexia, tachycardia, psychosis, sedation, dry mouth, ventricular irritability, postural hypotension, priapism rare, headaches, dry mouth, nausea, constipation, sexual dysfunction

Buspiron

Mechanism of action:

• Unclear

• May involve alteration of dopaminergic or serotinergic activity in CNS (partial agonist of the serotonin 5-HT1Areceptor)
• Nonsedating, doas’nt produce tolerance or dependence, doas’nt interact with BD receptor or alcohol
• Takes 1 month lag time before clinical response

;Requires thrice-daily dosing

Indications:

the same as the BD, generalized anxiety disorder, social phobias

Adverse effects: minimal sedation, nausea, headache, psychomotor impairment

Barbiturates

Effective sedative-hypnotics; Impairment of motor and intellectual performance; Interact with many drugs; High fatality rate with overdoses; High addiction potential

• Facilitate the actions of GABA at multiple sites in the CNS, but (in cotrast to BD) appear to increase the duration of the GABA-gated chloride channel openings

• At high concentrations may also be GABA-mimetic, directly activating chloride channels

• These effects involve a binding site (sites) distinct from BD binding site

• Also depress the actions of excitatory neurotransmitters (eg glutamic acid)

Antihistamines

• Hydroxizine – limited usefulness as a pre-anesthetic sedative (patients who do not respond to BD), Diphenhydramine

• Usually with effective dosage – sedation, increase muscle tone, lower seizure threshold, affect the peripheral nervous system

Antipsychotics
Not cosistently effective in treating anxiety; Seldom used to treat anxiety

Anticonvulsants

• GABAergic properties (gabapentin, oxcarbazepine, tiagabine, pregabalin, divalproex)

Beta-blokers

Effective in preventing performance anxiety by suppressing sympathetic nervous system activity and autonomic symptoms (palpitations, tremor);

Ineffective in preventing the emotional symptoms

Clonidine
Acts by decreasing the firing of locus ceruleus.

Side effects: dry mouth, increased tension, drowsiness, sleep disturbances;

Meprobamate and derivatives

• Muscle relaxant properties, sedative and anticonvulsant activity; Induce liver microsomal enzymes; Tolerance, dependence

Alcohol – The most common self-prescribed anxiolytic agent

• It is not recommended for use in the treatment of anxiety disorders (alcoholism)

Source: http://www.farmakologia.ump.edu.pl/attachments/

article/35/sedative%20and%20antianxiety%20~.doc

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