Posttraumatic Stress Disorder Medication
- Author: T Allen Gore, MD, MBA, CMCM, DFAPA; Chief Editor: Iqbal Ahmed, MBBS, FRCPsych(UK) more...
Many different drugs have been used to treat specific symptoms of posttraumatic stress disorder (PTSD), such as benzodiazepines for anxiety, anticonvulsants for impulsivity and emotional lability, and clonidine for nightmares. However, the principal agents of treatment have been the various antidepressants and beta-blockers.
Most medication trials on PTSD have involved male combat veterans. Results of studies on civilians show fluoxetine to be effective. Some studies suggest that fluoxetine demonstrates some efficacy for all 3 symptom clusters. Atypical antipsychotics have been used for patients who do not respond to antidepressants. Patients with severe PTSD symptoms are likely to need longer treatment to experience beneficial results from taking these medications. A study by Pollack et al suggests 3 mg of eszopiclone can improve in the short term, overall PTSD severity as well as improve sleep as compared with placebo. Further studies on eszopiclone are needed.
Novel pilot studies in combat veterans suggest alpha-1 antagonists have efficacy on the sleep-associated symptoms of PTSD. Alpha-1 antagonists have not been FDA approved for this indication; however, low-dose glucocorticoids may have a role in decreasing recall of traumatic memories, but further research is warranted.
Small, double-blind, placebo controlled studies have indicated that a nighttime dose of prazosin (10-15 mg) decreases nightmares and sleep disturbances in combat veterans with PTSD and increases normal dreaming patterns. Additional pilot trials have suggested that a midmorning dose of prazosin also helps to decrease daytime PTSD symptoms in civilian and military patients. However, larger, randomized, placebo-controlled trials are needed to confirm these results.
Selective serotonin reuptake inhibitors
The selective serotonin reuptake inhibitors (SSRIs) work by blocking the reuptake of serotonin. SSRIs such sertraline (Zoloft) and paroxetine (Paxil) have been FDA approved to treat PTSD as well as other disorders.
Sertraline is an SSRI that is FDA approved for the treatment of PTSD, panic disorder, social anxiety, and obsessive-compulsive disorder. It may be particularly useful in women who have experienced sexual or physical assaults.
Paroxetine is FDA approved to treat PTSD. It is used to reduce symptom severity of PTSD. It is a potent, selective inhibitor of neuronal serotonin reuptake. It also has a weak effect on norepinephrine and dopamine neuronal reuptake. It is also FDA approved for panic disorder, depression, social anxiety disorder, and obsessive-compulsive disorder.
Fluoxetine selectively inhibits presynaptic serotonin reuptake with minimal or no effect on the reuptake of norepinephrine or dopamine. SSRIs as fluoxetine have less sedation, cardiovascular, and anticholinergic effects than the tricyclic antidepressants (TCAs). Studies have shown this drug to be superior for measures of PTSD severity, disability, and high end-state function.
Monoamine oxidase inhibitors
The monoamine oxidase inhibitors work by inhibiting monoamine oxidase, which causes an increase in endogenous enzymes such as norepinephrine, epinephrine, serotonin, and dopamine.
Phenelzine is a nonselective monoamine oxidase inhibitor. In one double-blind, placebo-controlled trial, it was suggested that phenelzine was efficient in reducing intrusion symptoms. It has demonstrated clear superiority over placebo in double-blind trials for treating specific symptoms of panic disorders. This agent is usually reserved for patients who do not tolerate or respond to traditional cyclic or second-generation antidepressants.
TCAs are a class of antidepressants that work by inhibiting the reuptake of norepinephrine or serotonin at presynaptic neurons.
Amitriptyline is a TCA that is indicated for depression. Antidepressants have been used in the treatment PTSD; however, it is not FDA approved for this indication.
Imipramine is a TCA that is used to relieve the symptoms of depression. Antidepressants have been used in patients with PTSD and have shown beneficial effects. Imipramine is not FDA approved for the treatment of PTSD.
Benzodiazepines are useful in treating patients with PTSD who are also experiencing anxiety. They may also play a role in symptomatic relief of irritability, sleep disturbances, and other hyperarousal symptoms.
Lorazepam is a benzodiazepine and sedative hypnotic with a short onset of effects and a relatively long half-life. It can be used for the short-term relief of symptoms of anxiety. By increasing the action of gamma-aminobutyric acid (GABA), which is a major inhibitory neurotransmitter in the brain, it may depress all levels of the CNS, including limbic and reticular formation.
Diazepam is a benzodiazepine that modulates the postsynaptic effects of GABA-A transmission, resulting in an increase in presynaptic inhibition. It appears to act on part of the limbic system, thalamus, and hypothalamus to induce a calming effect. It may be used to provide short-term relief of symptoms of anxiety
Beta-blockers such as propranolol are useful in controlling some symptoms of PTSD caused by hyperarousal. A pilot study revealed propranolol is effective for decreasing physiological signs of hyperarousal for up to 1 week when used shortly after patients with PTSD reexperience their traumatic event. Ideally, propranolol is to be used within 6 hours of the initial traumatic event, well before a diagnosis of PTSD is made. Larger randomized, placebo-controlled studies are warranted to confirm these findings.
Propranolol is a nonselective beta-adrenergic receptor blocking agent. It has been found to relieve exaggerated startle response, explosiveness, nightmares, and intrusive reexperiencing in some patients with PTSD. Propranolol has not been FDA approved for these indications.
Anticonvulsants are commonly used in the treatment of bipolar disorder and epilepsy, as well as in patients with PTSD who are experiencing impulsivity and emotional liability. Several anticonvulsants have had positive data showing beneficial effects in PTSD; however, no anticonvulsants have been FDA approved for this disorder.
Carbamazepine is an anticonvulsant whose mechanism of action may involve depressing activity in the nucleus ventralis anterior of the thalamus, resulting in a reduction of polysynaptic responses and a blocking of posttetanic potentiation. It reduces sustained high-frequency repetitive neural firing. It has been studied in various trials for PTSD.
Triazine derivative used in neuralgia. Inhibits release of glutamate and inhibits voltage-sensitive sodium channels, leading to stabilization of neuronal membrane.
Several atypical antipsychotics have been studied in the treatment of PTSD. They may be helpful in alleviating the reexperiencing cluster of symptoms. These agents are not FDA approved for the treatment of PTSD. Antipsychotic agents may help patients with nightmares or flashbacks who have not responded to other treatment options.
A study by Krystal et al found no significant difference between atypical antipsychotics and placebo for antidepressant-resistant symptoms of military service – related PTSD. Observations were made over a 6-month period in 247 patients at 23 United States Veterans Administration outpatient medical centers.
Risperidone is an antipsychotic that is approved to treat patients with bipolar mania, schizophrenia, and irritability associate with autistic disorder. Atypical antipsychotics have been used for patients who do not respond to antidepressants.
Olanzapine is approved for the treatment of bipolar disorder, schizophrenia, and treatment-resistant depression. It has shown benefits in the treatment of PTSD; however, it is not FDA approved for this indication.
Alpha-1 Receptor Antagonists
Novel pilot studies in combat veterans suggest alpha-1 antagonists have efficacy on the sleep-associated symptoms of PTSD. Alpha-1 antagonists have not been FDA approved for this indication.
Prazosin is an alpha-1 adrenergic blocker that is indicated for hypertension. Studies indicate that a nighttime dose of prazosin (10-15 mg) decreases nightmares and sleep disturbances in combat veterans with PTSD and increases normal dreaming patterns. Additional pilot trials have suggested that a midmorning dose of prazosin also helps to decrease daytime PTSD symptoms in civilian and military patients. However, larger, randomized, placebo-controlled trials are needed to confirm these results.
Alpha-2 Adrenergic Agonists
Agents in this class may decrease vasomotor tone and heart rate by stimulating alpha2-adrenoreceptors in the brain stem and activating an inhibitory neuron.
Clonidine is a central alpha-adrenergic agonist that is commonly used as an antihypertensive agent. It stimulates alpha2-adrenoreceptors in the brain stem and activates an inhibitory neuron, resulting in a decrease in vasomotor tone and heart rate. Clonidine may have potential effects on the hyperarousal symptoms of PTSD. It may also help in patients experiencing nightmares.
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