Serotonin social anxiety disorder

Selective serotonin reuptake inhibitors (SSRIs) are considered the drugs of choice based on their tolerability and efficacy for social anxiety disorder as well as comorbid disorders. 

Serotonin-Boosting Antidepressants. The SSRIs have also been studied in the treatment of generalized social anxiety disorder, and paroxetine, sertraline, and venlafaxine are effective. Preliminary data suggests that the serotonin-boosting atypical antidepressants (mirtazapine and nefazodone) may also be helpful. Like the MAOIs, they appear to be effective at doses comparable to those used to treat depression. They may help avoidant patients to gradually increase their social interaction and become more assertive. 

This group includes compounds with actions on a range of neurotransmitter systems. Their antidepressant efficacy is mediated by reuptake inhibition of serotonin and noradrenaline, although side-effects such as sedation may also be useful. Their use in anxiety disorders is supported by a long history of clinical experience and a reasonable evidence base from controlled trials. Studies support the use of clomipramine (a potent serotonin reuptake inhibitor) in panic disorder and OCD (Lecrubier et al. 1997 Clomipramine Collaborative Study Group 1991), of imipramine in panic disorder and GAD (Cross-National Collaborative Panic Study 1992 Rickels et al. 1993), and of amitriptyline in PTSD (Davidson et al. 1993a). No controlled studies support the use of TCAs in social anxiety disorder. 

The generalized form of social anxiety disorder, on the other hand, is thought to be due to problems with dopamine and serotonin systems. Interestingly, people with Parkinson s disease, which is characterized by low levels of dopamine, are more likely to develop generalized social anxiety disorder. 

Also, a malfunction in the dopamine system has been shown to make it more likely for a person to have a detached personality, which is a characteristic of patients with social anxiety disorder. Serotonin systems are thought to be involved because SSRIs are effective in treating this form of the disorder. Although these systems have been implicated, little is known about how they are malfunctioning to produce the symptoms that characterize this problem. 

Clinicians will readily recognize in Table 3.7 the experiences reported by many of their patients when receiving treatment for depression or other related psychiatric disorders. By looking at the Function affected column, it is possible to understand why some medications (say, SSRIs) are effective in variable degrees in several conditions associated with serotonin dysfunction (depression, OCD, social anxiety disorder, posttraumatic stress disorder, generalized anxiety disorder, panic disorder, and bulimia nervosa). 

Stein MB, Seedat S, Gelernter J. Serotonin transporter gene promoter polymorphism predicts SSRI response in generalized social anxiety disorder. Psy chopharmacol 2006 187 68-72. 

The selective serotonin reuptake inhibitors or venlafaxine are considered first-line pharmacotherapy for social anxiety disorder, especially in patients with comorbid depression, other anxiety disorders, or substance abuse. 

FIGURE 69-3. Algorithm for the pharmacotherapy of social anxiety disorder. SSRI = selective serotonin reuptake inhibitor, BZ = benzodiazepine. (Compiled from Ballenger et al, Van Amerigen and Mancini, and Blanco... 

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). 

Venlafaxine is a serotonin and norepinephrine reuptake inhibitor that potentiates norepinephrine, serotonin, and dopamine neurotransmitter activity in the CNS by inhibiting their neuronal reuptake. Effexor, Effexor XR are used in treatment of major depressive disorder. Effexor XR is used in treatment of generalized anxiety disorder and treatment of social anxiety disorder. 

Sertraline hydrochloride was introduced to the market by Pfizer and known under the brand names Zoloft and Lustral. Sertraline is an antidepressant " " of the selective serotonin reuptake inhibitor (SSRI) class and is primarily used to treat major depression, highly effective for the treatment of panic and social anxiety disorders. ... 

Sertraline hydrochloride (known under the trade names Zoloft and Lustral, both from Pfizer) is an antidepressant chiral drug acting as a selective serotonin reuptake inhibitor (SSRI). It is primarily used in major depression treatment and as obsessive/compulsive, panic, and social anxiety disorders. Ir-Catalyzed enantioselective hydrogenation of C=N bond can be employed to install a second stereogenic... 

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. 

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. 

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. 

The anxiolytic activity of several compounds in some, but not all, animal models of anxiety in fact suggests that different receptor subtypes may modulate different types of anxiety as discussed below. It would not be surprising if the specific serotonin links to disorders of anxiety also differ among the various disorders of anxiety such as generalized anxiety versus obsessive-compulsive disorder versus panic disorder versus social phobia versus mixed anxiety depression. Such studies are in progress, and much further research is necessary to clarify the potential links between subtypes of anxiety and subtypes of serotonin receptors. 

Paroxetine. Paroxetine, also a serotonin reuptake inhibitor, has been the subject of a case report in two subjects. Ringold [1994] reported the effective treatment of two individuals who had not responded to prior therapy with fluoxetine and sertraline. Both individuals had comorbid psychiatric problems. Subject A demonstrated both social phobia and dysthymia. Although her symptoms of dysthymia were clinically responsive to fluoxetine therapy, her social phobia symptoms were resistant. Subject B had body dysmorphic disorder, obsessive-compulsive disorder, and social phobia. His obsessive-compulsive disorder symptoms benefited from fluoxetine therapy, but his social anxiety was resistant. Sertraline therapy was attempted in both subjects. Subject A required discontinuation because of adverse effects. Subject B experienced a worsening of both obsessive-compulsive disorder and social phobia symptoms. Both subjects demonstrated a positive response in their symptoms when switched to paroxetine [20 mg/day]. 

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... 

SSRIs show efficacy in social phobia, and combined serotonin and norepinephrine uptake inhibitors are effective in generalized anxiety disorder. 

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