Serotonin post-traumatic stress

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. 

The full complement of anxiety syndromes including panic, generalized anxiety, obsessive-compulsiveness, and post-traumatic stress disorder can arise in the after-math of TBI. In fact, anxiety may be the most common neuropsychiatric complication of TBI. Anxiety appears to be most likely to arise when the injury occurs to the right side of the brain. The treatment alternatives for post-TBl anxiety parallel those used when treating anxiety disorders and include serotonin-boosting antidepressants, buspirone (Buspar), and the benzodiazepines (see Table 12.1). 

In addition to their proven efficacy in the treatment of all types of depression, the SSRIs have been shown to be the drugs of choice in the treatment of panic disorder, obsessive-compulsive disorder, bulimia nervosa, and as an adjunct to the treatment of alcohol withdrawal and relapse prevention, premenstrual dysphoric disorder and post-traumatic stress disorder. The usefulness of these drugs in treating such a diverse group of disorders reflects the primary role of serotonin in the regulation of sleep, mood, impulsivity and food intake. 

In recent years many of these primary care cases that would formerly have been seen as anxiety disorders have been portrayed as anxious-depressives and have led to treatment with antidepressants, in particular the more recent serotonin reuptake inhibitors. As part of this rebranding a variety of states such as panic disorder, post-traumatic stress disorder, social phobia and generalized anxiety disorder have appeared, along with more traditional disorders such as obsessive compulsive disorder (OCD). Many of these diagnoses are likely to lead to prescriptions of an SSRI although the evidence for benefit from SSRIs is poor except for OCD. 

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

DA, dopamine DD, depressive disorders (major depression and/or dysthymia) DZ, dizygotic twins 5-HT, serotonin p-CIT, iodine-123-labeled 2p-carbomethoxy-3p(iodophenyl) tropane MDD,major depressive disorder MRI, magnetic resonance imaging MZ, monozygotic twins NC, normal controls PC, psychiatric controls PTSD post-traumatic stress disorder rCBF, regional cerebral blood flow SPECT, single photon emission computerized tomography Tc HMPAO, technetium-99m hexamethylpropylene amine oxime. 

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. 

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)... 

The mood and anxiety disorders in their various permutations constitute a major source of personal suffering and impaired ability to engage in productive Avork and interpersonal relationships. Between 5 and 9% of women and between 2 and 3% of men meet the diagnostic criteria for major depression at any time 10-25% of all women suffer major depression sometime in their lives, while 5-10% of men will develop major depressive disorder (American Psychiatric Association, 1994). The anxiety disorders obsessive-compulsive disorder (OCD), post-traumatic stress disorder (PTSD), panic disorder, and generalized anxiety disorder (GAD) show lifetime prevalence rates of approximately 2.5%, 7%, 2.5%, and 5% respectively. Between 3 and 13% of individuals in community samples are regarded to meet the diagnostic criteria for social phobia. Mood and anxiety disorders are common comorbidities (American Psychiatric Association, 1994) and the most common antidepressant medications including the serotonin reuptake inhibitors, the mixed serotonin-catecholamine reuptake inhibitors, the tricyclic antidepressants, and the monoamine oxidase inhibitors, are all effective treatments for anxiety and panic attacks. 

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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