Serotonin and aggression panic attack and related disorders

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The possible overlap between anxiety, depression, panic attack, aggression and obsessive-compulsive disorders, and the involvement of serotonin in the symptoms of these disorders, has recently led to the investigation of various selective serotonin reuptake inhibitors (SSRIs) and selective 5-HT receptor agonists/antagonists in the treatment of these conditions. In experimental studies, there is evidence that drugs such as eltoprazine, which binds with high affinity to 5-HT1A, 5-HT1B and 5-HT2c sites, are active antiaggressive agents, whereas selective 5-HT1A agonists and 5-HT2 and 5-HT3 antagonists are inactive. There is also preliminary evidence to suggest that SSRIs such as fluoxetine reduce impulsive behaviour which may contribute to their therapeutic action in the treatment of obsessive-compulsive disorders and possibly in reducing suicidal attempts.

Zohar and Insel have suggested that the symptoms of obsessive-compulsive disorder are due to supersensitive 5-HT1-type receptors and that the function of SSRIs such as clomipramine, fluoxetine and the non-selective 5-HT antagonist metergoline owe their efficacy to their ability to reduce the activity of these receptors.

It now seems generally accepted that the effects of anti-obsessional drugs may be mediated by serotonergic mechanisms. The apparent hypersensitivity of obsessive-compulsive patients to the trazodone metabolite m-chlorophenyl piperazine (mCPP, a non-selective 5-HT1B, 5-HT2C and 5-HT2 agonist) suggests that a diverse group of 5-HT1 and 5-HT2 receptors are involved. The efficacy of buspirone, a partial agonist of 5-HT1A receptors, in attenuating the obsessional symptoms further suggests that 5-HT1A receptors are also involved. As the 5-HT reuptake inhibitors such as fluoxetine and fluvoxamine are particularly effective in attenuating the obsessive symptoms following several weeks of administration, it may be argued that the therapeutic effect of such drugs lies in their ability to desensitize the supersensitive 5-HT1-type receptors. Which of the 5-HT1 receptors is specifically involved is unclear, but neuroimaging studies on patients with obsessive-compulsive disorder implicate the striatum as the major brain region which is defective. The 5-HT receptors in the striatum are 5-HT1D and 5-HT2 in man which may implicate these receptor subtypes specifically in the aetiology of the condition.

With regard to generalized anxiety disorder, it has been postulated that an overactivity of the stimulatory 5-HT pathways occurs. Drugs such as buspirone and ipsapirone are effective in such conditions because they stimulate the inhibitory 5-HT1A autoreceptors on the raphe nuclei and thereby reduce serotonergic function. It is noteworthy that the SSRIs often worsen anxiety initially because they temporarily enhance serotonergic function. Adaptive changes in the pre- and postsynaptic 5-HT receptors then occur leading to a reduction in the anxiety state.

A further discussion of the pharmacological properties of the anxiolytic drugs is given in Chapter 9.

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Do Not Panic

Do Not Panic

This guide Don't Panic has tips and additional information on what you should do when you are experiencing an anxiety or panic attack. With so much going on in the world today with taking care of your family, working full time, dealing with office politics and other things, you could experience a serious meltdown. All of these things could at one point cause you to stress out and snap.

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