Selective serotonin reuptake inhibitors in the treatment of generalized anxiety disorder

Abstract

Selective serotonin reuptake inhibitors have proven efficacy in the treatment of panic disorder, obsessive-compulsive disorder, post-traumatic stress disorder and social anxiety disorder. Accumulating data shows that selective serotonin reuptake inhibitor treatment can also be efficacious in patients with generalized anxiety disorder. This review summarizes the findings of randomized controlled trials of selective serotonin reuptake inhibitor treatment for generalized anxiety disorder, examines the strengths and weaknesses of other therapeutic approaches and considers potential new treatments for patients with this chronic and disabling anxiety disorder. Expert Rev. Neurotherapeutics 2(5), 717-724 (2002) † Author for correspondenceUniversity Department of Mental Health, Royal South Hants Hospital, Southampton SO14 0YG, UK Tel.: +44 2380 825533 Fax: +44 2380 KEYWORDS:citalopram, escitalopram, fluoxetine, fluvoxamine, GAD, paroxetine, sertraline, SSRI Introductory overview Clinical features & epidemiology of generalized anxiety disorderGeneralized anxiety disorder (GAD) is characterized by inappropriate or excessive anxiety and worrying that is persistent and not restricted to particular circumstances. Common symptoms include:• Apprehension, with worries about future misfortune • Inner tension and difficulty in concentrating; motor tension, with restlessness • Tremor and headache • Autonomic anxiety, with excessive perspiration, dry mouth and epigastric discomfortThe lifetime prevalence in the general population is around 5-6%, the 12-month prevalence varying according to diagnostic criteriafrom 1.5% with Diagnostic and Statistical Manual of Mental Disorders IV (DSM-IV) to 3.1% with DSM-III-R criteria [1]. The age of onset of GAD differs from that with other anxiety disorders, the majority of cases presenting aged around 35-45 years [2][3][4]. GAD is probably the most common anxiety disorder among the elderly population (55-85 years) [5]. Symptoms fluctuate in intensity over time, but GAD is usually a chronic condition [6]. The functional impairment is similar in magnitude to that with major depression [3,7].GAD is amongst the most common psychiatric disorders seen in general practice. The point prevalence of ICD-10 defined GAD in European primary care settings was 4.8% for GAD without other comorbid depressive or anxiety disorders and 3.7% for GAD with depression: a further 4.1% had 'subthreshold' GAD [6]. Comorbid GAD is associated with more severe symptoms, greater functional impairment, a more prolonged course, decreased productivity and higher use of health services [6][7][8][9]. Comorbid depressive symptoms improve the chances of a patient being recognized as having a psychological problem, though not necessarily GAD [6]. Pathophysiology of generalized anxiety disorderSerotonin (5-hydroxytryptamine, 5-HT) is integrally involved in the mediation of anxiety through serotonergic innervation of the limbic system, hypothalamus and thalamus. Levels of the serotonin metabolite 5-hydroxyindoleacetic acid in c...

Reversal of reserpine-induced depression and cognitive disorder in zebrafish by sertraline and Traditional Chinese Medicine (TCM)

“…SSRIs selectively inhibit the reuptake of 5-HT by the presynaptic membrane. SSRIs have little impact on NA and hardly affect the reuptake of DA [ 51 ]. In our study, the reserpine-induced zebrafish model of depression showed increased whole-body cortisol and 5-HT, decreased NA and reduced TH.…”

Case-Control Study Examining the Association between Selective Serotonin Reuptake Inhibitors Use and Hepatocellular Carcinoma

“…Selective serotonin reuptake inhibitors are used to treat major depressive disorder and anxiety disorder ( Hirschfeld, 2000 ; Baldwin et al, 2002 ; Hedges et al, 2007 ). Recently, an in vitro study showed that selective serotonin reuptake inhibitors seemed to have anti-tumor effects on human hepatocellular carcinoma ( Kuwahara et al, 2015 ).…”

1- or 3-(3-Amino-2-hydroxy-1-phenyl propyl)-1,3-dihydro-2H-benzimidazol-2-ones: Potent, Selective, and Orally Efficacious Norepinephrine Reuptake Inhibitors

“…The serotonin (SERT a Abbreviations: NE, norepinephrine; NET, norephinephrine transporter; NRI, norepinephrine reuptake inhibitor; 5-HT, serotonin; SERT, serotonin transporter; SRI, serotonin reuptake inhibitor; SNRI, serotonin and norepinephrine reuptake inhibitor; DA, dopamine; DAT, dopamine transporter; hNET, human norepinephrine transporter; hSERT, human serotonin transporter; hDAT, human dopamine transporter; MDD, major depressive disorder; SUI, stress urinary incontinence; ADHD, attention deficit hyperactivity disorder; SAR, structure−activity relationship; AUC, area under the curve; C max , maximum concentration; OVX, ovariectomized; TST, tail-skin temperature; SNL, spinal nerve ligation. ), norepinephrine (NET), and dopamine transporters (DAT) are integral membrane proteins that uptake 5-hydroxytryptamine (5-HT, serotonin), norepinephrine (NE), and dopamine (DA), respectively, into presynaptic cells from the synaptic cleft and play a critical role in regulating the physiological functions of these neurotransmitters. , Monoamine neurotransmitter deficiency has been implicated in a number of neurological disorders making transporter inhibitors potential treatment for a wide range of CNS diseases. Since the early 1980s, numerous monoamine reuptake inhibitors, including selective serotonin reuptake inhibitors (SRIs), norepinephrine reuptake inhibitors (NRIs), and dual serotonin and norepinephrine reuptake inhibitors (SNRIs), have been developed for the treatment of psychiatric disorders. , Selective SRIs and NRIs such as fluoxetine and reboxetine ( 1 ) have been used to treat symptoms including major depression and anxiety disorders. − Additionally, clinical evidence also suggested that reboxetine may have efficacy in the treatment of chronic pain such as fibromyalgia and chronic low back pain . Atomoxetine ( 2 ), another selective NRI, has been approved for attention deficit hyperactivity disorder (ADHD) .…”

“…3,4 Selective SRIs and NRIs such as fluoxetine and reboxetine (1) have been used to treat symptoms including major depression and anxiety disorders. [5][6][7] Additionally, clinical evidence also suggested that reboxetine may have efficacy in the treatment of chronic pain such as fibromyalgia and chronic low back pain. 8 Atomoxetine (2), another selective NRI, has been approved for attention deficit hyperactivity disorder (ADHD).…”