Obsessive-compulsive disorder dysfunction

SSRIs are well tolerated. Adverse effects for compounds in this class include nervousness, tremor, dizziness, headache, insomnia, sexual dysfunction, nausea, and diarrhea. In addition, the tricycHc antidepressant clomipramine (33), which is a potent nonselective serotonin reuptake inhibitor, is approved for treatment of obsessive—compulsive disorder. 

SSRIs are widely used for treatment of depression, as well as, for example, panic disorders and obsessive—compulsive disorder. These dmgs are well recognized as clinically effective antidepressants having an improved side-effect profile as compared to the TCAs and irreversible MAO inhibitors. Indeed, these dmgs lack the anticholinergic, cardiovascular, and sedative effects characteristic of TCAs. Their main adverse effects include nervousness /anxiety, nausea, diarrhea or constipation, insomnia, tremor, dizziness, headache, and sexual dysfunction. The most commonly prescribed SSRIs for depression are fluoxetine (31), fluvoxamine (32), sertraline (52), citalopram (53), and paroxetine (54). SSRIs together represent about one-fifth of total worldwide antidepressant unit sales. 

Obsessive-compulsive disorder is a disorder of the frontal-subcortical system. A characteristic of this group of disorders is a complex interaction between the exogenous and endogenous stimuli and the neural systems that link stimuli to cognitive and behavioral responses. Although cortical dysfunction cannot be excluded as a basis for OCD symptoms, there is evidence that basal... 

Hollander, E., Schiffman, E., Cohen, B., Rivera-Stein, M.A., Rosen, W., Gorman, J.M., Fyer, A.J., Papp, L., and Liebowitz, M.R. (1990) Signs of central nervous system dysfunction in obsessive-compulsive disorder. Arch Gen Psychiatry, 47 27-32. 

Modell, J.G., Mountz, J.M., Curtis, G.C., and Greden, J.E (1989) Neurophysiologic dysfunction in basal ganglia/limbic striatal and thalamocortical circuits as a pathogenetic mechanism of obsessive-compulsive disorder. / Neuropsychiatry Clin Neurosci 1 27-36. 

Golden RN, Morris JE, Sack DA Combined lithium-tricyclic treatment of obsessive-compulsive disorder. Biol Psychiatry 23 181-185, 1988 Goldenberg G, Lang W, Podreka 1, et al Are cognitive deficits in Parkinson s disease caused by frontal lobe dysfunction Journal of Psychophysiology 4 137-144, 1990 Goldgaber D, Harris HW, Hla T Interleukin-1 regulates synthesis of amyloid beta-protein precursor mRNA in human endothelial cells. Proc Natl Acad Sci U S A 86 7606-7610, 1989... 

Hollander E, Schiffman E, Cohen B, et al Signs of central nervous system dysfunction in obsessive-compulsive disorder. Arch Gen Psychiatry 47 27-32, 1990b Hollander E, Mullen L, DeCaria CM, et al Obsessive compulsive disorder, depression, and fluoxetine. J Clin Psychiatry 52 418-422, 1991 Hollander E, De Caiia CM, Nitescu A, et al Serotonergic function in OCD. Arch Gen Psychiatry 49 21-28, 1992... 

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)... 

Obsessive-compulsive disorder may be linked to abnormalities of the neurotransmitters serotonin and dopamine. The neuroanatomical basis of OCD may be related to dysfunction in the basal ganglia. The hallmark of treatment for OCD is use of SSRIs plus the tricyclic antidepressant clomipramine. Panic disorder is characterized by unexpected panic attacks, possibly linked to abnormalities in the neurotransmitters norepinephrine and GABA, in the sensitivity of benzodiazepine receptors, or even in the regulation of respiration. Drag treatments include SSRIs, several of the newer antidepressants, high-potency benzodiazepines, many tricyclic antidepressants, and MAO inhibitors. 

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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