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Coping with Anxiety and Phobi... Health Article

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Comparing medication and psychosocial therapies

Many different medications and therapies are used to control anxiety disorders. Most anxiety disorders improve dramatically with a combination of medication and cognitive behavioral therapy. But little is known about the relative effectiveness of medical and psychological approaches. Research sponsored by the National Institute of Mental Health is comparing how well drug and behavioral therapies work separately and together to treat obsessive-compulsive disorder. Studies such as this will help determine whether combination therapy can reduce the high relapse rate of people with obsessive-compulsive disorder.

Developing benzodiazepines and antidepressants

The goal of new drug development is to find agents that are at least as effective as those available today, with fewer adverse effects. These medications would be especially welcome for older adults and others who have trouble tolerating the side effects of existing drugs.

Safer benzodiazepines are of particular interest because these medications work quickly and are quite effective. One strategy has been to create partial agonists, drugs that affect only those parts of the benzodiazepine-GABA receptors that bring about therapeutic benefit. Several partial benzodiazepine receptor agonists have been tested in clinical trials.

Other investigators are developing more selective SSRIs. Like the partial benzodiazepine receptor agonists, these agents would bind to some but not all serotonin receptors. At least 14 different serotonin receptors have been identified, and studies show that four of them play a role in controlling anxiety.

Other types of drugs

Other kinds of drugs are being developed to act on the many other receptors and neurotransmitters that help promote or relieve anxiety. In early clinical studies, four targets look promising:

Neuropeptide Y agonists. Neuropeptide Y is an amino acid found throughout the nervous system. Human studies suggest that it has powerful anti-anxiety properties. Drugs that mimic its natural activity in the amygdala and other areas of the brain could help control anxiety symptoms.

Substance P antagonists. Researchers believe that substance P, a brain chemical present in the amygdala, plays a role in anxiety. Drugs that block substance P are being studied in clinical trials sponsored by the National Institute of Mental Health.

Corticotropin-releasing factor (CRF) antagonists. CRF is a hormone that activates the HPA axis to launch the stress response. Elevated amounts of this chemical have been found in people with post-traumatic stress disorder. Therefore, drugs that block its action might be useful in treating this condition.

Cholecystokinin antagonists. Cholecystokinin, another neurotransmitter found throughout the brain, is believed to prompt anxiety and panic attacks. In preliminary studies, agents that block cholecystokinin were given to healthy volunteers, as well as to people with panic disorder. Afterward, researchers tried to induce panic attacks experimentally, but none of the participants who had taken the cholecystokinin antagonist had panic attacks.

Glossary

adrenal glands: Two glands on top of the kidneys that secrete the hormones cortisol and norepinephrine.

agoraphobia: Fear and avoidance of open spaces and public spaces.

amygdala: A region of the brain that processes emotionally charged memories, including fear.

autonomic nervous system: The set of nerve pathways, starting with the hypothalamus in the brain, that controls vital functions like heart rate, body temperature, and blood pressure. It includes the sympathetic and parasympathetic nervous systems.

axon: The part of a neuron that carries impulses and stores neurotransmitters that convey signals to other neurons.

benzodiazepines: Medications that work by attaching to benzodiazepine-GABA receptors, helping to maintain levels of the neurotransmitter GABA in the brain.

brain imaging: A variety of technologies, such as magnetic resonance imaging (MRI), functional MRI (fMRI), and positron emission tomography (PET), used to examine the structure or function of the brain.

cognitive behavioral therapy: A form of therapy designed to correct ingrained patterns of negative thoughts or behaviors.

corticotropin-releasing factor (CRF): A hormone secreted by the hypothalamus that helps rouse the body to defend against a physical or emotional threat.

cortisol: A glucocorticoid, or steroid hormone, released by the adrenal glands. It helps trigger the "fight-or-flight" response and similar responses.

dendrites: The parts of a neuron that receive signals sent via neurotransmitters from other neurons.

gamma-aminobutyric acid (GABA): Chief inhibitory neurotransmitter in the brain. As an inhibitory neurotransmitter, it instructs the next neuron not to fire. GABA may help quell anxiety.

hippocampus: Part of the brain that plays a central role in processing long-term memories. It is smaller than normal in some people with post-traumatic stress disorder.

hypothalamic-pituitary-adrenal (HPA) axis: A system that governs a multitude of hormonal activities, including the body's response to stress.

hypothalamus: Part of the brain that regulates vital body functions (such as blood pressure and temperature). It receives signals from the body and secretes hormones that influence the production of other hormones.

limbic system: A group of brain structures associated with emotions, such as anger, pleasure, sorrow, fear, and sexual arousal.

locus ceruleus: An area of the brainstem that helps determine which stimuli are worth paying attention to. A malfunction of the locus ceruleus may contribute to anxiety.

neuron: A nerve cell.

neurotransmitters: Chemicals such as serotonin or norepinephrine that convey messages across the gap, or synapse, between adjoining neurons.

norepinephrine: A neurotransmitter that plays a role in the regulation of anxiety, mood, and responses to stress. Sometimes called noradrenaline.

pituitary gland: An endocrine gland tucked into a bony space beneath the brain. It receives input and influence from the hypothalamus. It produces adrenocorticotropic hormone (ACTH), which controls the secretion of cortisol by the adrenal glands. This helps trigger the "fight-or-flight" response.

selective serotonin reuptake inhibitors (SSRIs): Antidepressants that block the reabsorption of serotonin by the neurons that release it, leaving more serotonin available to nerve cell receptors.

serotonin: A neurotransmitter involved in regulating moods, sleep, and appetite, and inhibiting pain.

synapse: A tiny gap between neurons that neurotransmitters cross in conveying nerve impulses.