Selective Serotonin stress disorder

Indeed, 5-HT is also a substrate for the 5-HT transporter, itself an important player in the treatment of depression, and more recently for the whole range of anxiety disorders spectrum (GAD, OCD, social and other phobias, panic and post-traumatic stress disorders). It is the target for SSRIs (selective serotonin reuptake inhibitors) such as fluoxetine, paroxetine, fluvoxamine, and citalopram or the more recent dual reuptake inhibitors (for 5-HT and noradrenaline, also known as SNRIs) such as venlafaxine. Currently, there are efforts to develop triple uptake inhibitors (5-HT, NE, and DA). Further combinations are possible, e.g. SB-649915, a combined 5-HTia, 5-HT1b, 5-HT1d inhibitor/selective serotonin reuptake inhibitor (SSRI), is investigated for the treatment of major depressive disorder. 

Hidalgo, R.B. and Davidson, J.R. (2000) Selective serotonin reuptake inhibitors in post-traumatic stress disorder. J Psychopharmacol 14 70-76. 

The selective serotonin reuptake inhibitors (SSRI) have been used in adults for a wide variety of disorders, including major depression, social anxiety (social phobia), generalized anxiety disorder (GAD), eating disorders, premenstrual dysphoric disorder (PMDD), post-traumatic stress disorder (PTSD), panic, obsessive-compulsive disorder (OCD), trichotillomania, and migraine headaches. Some of the specific SSRI agents have an approved indication in adults for some of these disorders, as reviewed later in this chapter. The SSRIs have also been tried in children and in adults for symptomatic treatment of pain syndromes, aggressive or irritable ( short fuse ) behavior, and for self-injurious and repetitive behaviors. This chapter will review general aspects of the SSRIs and discuss their approved indications in children and adolescents. 

FDA, Food and Drug Administration GAD, general anxiety disorder OCD, obsessive-compulsive disorder PMDD, Premenstrual dysphoric disorder PTSD, post-traumatic stress disorder SRI, serotonin reuptake inhibitor SSRI, selective serotonin reuptake inhibitor. 

The efficacy of beta-blockers in the symptomatic relief of anxiety in adults has been established in over a dozen controlled trials (Neppe, 1989). In a number of countries, beta-blockers have been licensed for the treatment of anxiety disorders. Somatic manifestations of anxiety such as palpitations, diaphoresis, and tremor, rather than core psychological symptoms, were particularly responsive to beta-blocker treatment. In comparative trials that included patients with severe anxiety and panic attacks, the antianxiety effect of beta-blockers was, however, somewhat less powerful than that of benzodiazepines (Lader, 1988), with the exception of a small trial that compared alprazolam to propranolol (Ravaris et ah, 1991). Head-to-head comparisons of beta-blockers and selective serotonin reuptake inhibitors (SSRIs) are lacking. Performance and stress-related anxiety that may affect public performers, such as musicians or people taking an examination or giving a speech, seems to be particularly suited for beta-blocker treatment (Lader, 1988). Beta-blockers may be given on an as-required basis 1-2 hours before the stressful situation. 

Fluoxetine Highly selective blockade of serotonin transporter (SERT) little effect on norepinephrine transporter (NET) Acute increase of serotonergic synaptic activity slower changes in several signaling pathways and neurotrophic activity Major depression, anxiety disorders panic disorder obsessive-compulsive disorder post-traumatic stress disorder perimenopausal vasomotor symptoms eating disorder (bulimia) Half-lives from 15-75 h oral activity Toxicity Well tolerated but cause sexual dysfunction Interactions Some CYP inhibition (fluoxetine 2D6, 3A4 fluvoxamine 1A2 paroxetine 2D6)... 

By the 1990s antidepressants from the serotonin selective reuptake inhibitor (SSRI) class became recognized as preferred first-line treatments for anxiety disorder subtypes, ranging from obsessive-compulsive disorder, to panic disorder, and now to social phobia and posttraumatic stress disorder (Fig. 8—9). Not all antidepressants, however, are afficacious anxiolytics. For example, desipramine and bupropion seem to be of little help in several anxiety disorder subtypes. Documentation of efficacy... 

Table 5.4 Recommended doses of selective serotonin reuptake inhibitors (SSRIs) for treating posttraumatic stress disorder...

Selective serotonin reuptake inhibitors (SSRIs) A relatively new group of medicines that have been used successfully to treat emotional and behavioral problems such as depression, panic disorder, obsessive-compulsive disorder ((XID), bulimia, and posttraumatic stress disorder in adults. These medications are now being used to treat the same types of behavior in children. Some examples of SSRIs include Prozac (fluoxetine), Zoloft (sertraline), Luvox (fluvoxamine), and Paxil (paroxetine). 

National Institute of Drug Abuse National Institutes of Health National Institute of Mental Health posttraumatic stress disorder selective serotonin reuptake inhibitor State University of New York... 

Paroxetine is a selective serotonin reuptake inhibitor that blocks reuptake of serotonin, enhancing serotonergic function. It is used to treat panic disorder or social anxiety disorder (except Pexeva), as defined in the DSM-IV major depressive disorder, as defined in DSM-111 (immediate release) orDSM-lV (controlled release). Immediate release only for obsessive-compulsive disorder (OCD) generalized anxiety disorder (GAD) (except Pexeva) posttraumatic stress disorder (PTSD), as defined in the DSM-IV (except Pexeva). 

When compared with the selective serotonin reuptake inhibitors (SSRIs), mirtazapine may show an earlier onset of action (although data are currently not well established). Mirtazapine has also been found to be efficacious in the treatment of elderly patients with depression. Mirtazapine has been shown to be effective in the treatment of panic disorder, social phobia, and post-traumatic stress disorder. In one study, mirtazapine combined with citalopram in obsessive-compulsive patients induced an earlier response when compared with citalopram plus placebo. It was suggested that antagonism of presynaptic a2-adrenergic receptors does not enhance serotonin neurotransmission directly, but rather disinhibits the norepinephrine activation of serotonergic neurons and thereby increases serotonergic neurotransmission by a mechanism that may not require a time-dependent desensitization of receptors. 

In 1987, the United States Food and Dmg Administration (FDA) approved the use of fluoxetine for the treatment of depression and this derivative is now considered to be the prototype of a dmg class called selective serotonin reuptake inhibitors (SSRIs). As the name suggests, this term refers to the reuptake blockage of serotonin into the pre-synaptic membrane in order to indirectly increase neurotransmitter availability. A number of these derivatives showed beneficial effects for the treatment of a variety of additional conditions such as obsessive-compulsive disorders (OCD), bulimia nervosa, anxiety disorders, obesity, anorexia, post-traumatic stress disorders (PTSD) and others. SSRIs have become the first-line therapy for depression, which is based on improved side effect profiles when compared with TCA derivatives or MAOIs. A number of adverse effects are described in the pharmacological literature and include sexual dysfunction. 

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