Mood disorders effects

G-protein-coupled cyclic AMP signaling in postmortem brain of subjects with mood disorders effects of diagnosis, suicide, and treatment at the time of death. J. Neurochem. 73, 1121-26. 

Treatment of Manic—Depressive Illness. Siace the 1960s, lithium carbonate [10377-37-4] and other lithium salts have represented the standard treatment of mild-to-moderate manic-depressive disorders (175). It is effective ia about 60—80% of all acute manic episodes within one to three weeks of adrninistration. Lithium ions can reduce the frequency of manic or depressive episodes ia bipolar patients providing a mood-stabilising effect. Patients ate maintained on low, stabilising doses of lithium salts indefinitely as a prophylaxis. However, the therapeutic iadex is low, thus requiring monitoring of semm concentration. Adverse effects iaclude tremor, diarrhea, problems with eyes (adaptation to darkness), hypothyroidism, and cardiac problems (bradycardia—tachycardia syndrome). 

In noncancer-related pharmacology, GSK3 is inhibited by lithium at therapeutic concentrations, implying that the long-established effectiveness of lithium in the treatment of psychiatric mood disorders (and more recently as a neuroprotective agent) may be linked to GSK3 inhibition. Antipsychotics such as haloperidol... 

Tricyclic antidepressants (TCAs) such as amitriptyline and doxepin have been used with some success in the treatment of IBS-related pain (Table 18-5). They modulate pain principally through their effect on neurotransmitter reuptake, especially norepinephrine and serotonin. Their helpfulness in functional gastrointestinal disorders seems independent of mood-altering effects normally associated with these agents. Low-dose TCAs (e.g., amitriptyline, desipramine, or doxepin 10 to 25 mg daily) may help patients with IBS who predominantly experience diarrhea or pain. 

The clinical significance of this ethnic difference for psychiatry was found later. A study examining lithium tolerability found more side effects in African American patients with high RBC/plasma ratio even when the lithium levels were in the therapeutic range (Strickland etal., 1995). It is not known whether African Americans require lower doses and will respond with lower plasma levels. We do know that African Americans with mood disorders are less likely to be prescribed lithium either as primary treatment or adjunctive therapy (Valenstein etal., 2006 Kilbourne 8c Pincus, 2006). It is unknown as to whether the lack of tolerability at usual therapeutic doses is a factor. 

Serretti, A., Cusin, C., Rossini, D. et al. (2004). Further evidence of a combined effect of SERTPR and TPH on SSRIs response in mood disorders. Am. J. Med. Genet. B Neuropsychiatr. Genet., 129B(1), 36-40. 

Leonard BE and Richelson E (2000). Synaptic effects of antidepressants Relationships to their therapeutic and adverse effects. In PF Buckley and JL Waddington (eds), Schizophrenia and Mood Disorders (pp. 67-84). Butterworth-Heinemann, Oxford, UK. 

Non-motor signs of the disorder are also treatable with symptomatic medications. The frequent mood disorder can be treated with standard antidepressants, including tricyclics (such as amitryptiline) or serotonin reuptake inhibitors (SSRIs, such as fluoxetine or sertraline). This treatment is not without risks in these patients, as it may trigger manic episodes or may even precipitate suicide. Anxiety responds to benzodiazepines, as well as to effective treatment of depression. Long-acting benzodiazepines are favored over short-acting ones because of the lesser abuse potential. Some of the behavioral abnormalities may respond to treatment with the neuroleptics as well. The use of atypical neuroleptics, such as clozapine is preferred over the typical neuroleptics as they may help to control dyskinesias with relatively few extrapyramidal side-effects (Ch. 54). 

There is ample support for the hypothesis of noradrenergic system dysfunction in depression however, the inconsistencies in findings rule out any simple model of increased or decreased noradrenergic activity. It is important to determine which noradrenergic system abnormalities relate specifically to the pathogenesis of mood disorders, and which are related to nonspecific effects of stress, homeostatic mechanisms, or comorbid psychopathology. More work is needed on the mood-state-depen-dence of noradrenergic function. 

Thus, it is possible that recurrent mood disorders, as in the case of bipolar disorder, may lower the threshold for cell death and/or atrophy in response to a variety of other physiological (e.g. normal aging) and pathological (e.g. ischemic) events, and thereby contribute to a variety of deleterious health-related effects. 

Lamotrigine is effective for the maintenance treatment of bipolar I disorder in adults. It has both antidepressant and mood-stabilizing effects, and it may have augmenting properties when combined with lithium or valproate. It has low rates of switching patients to mania. Although it is less effective for acute mania compared to lithium and valproate, it may be beneficial for the maintenance therapy of treatment-resistant bipolar I and II disorders, rapidcycling, and mixed states. It is often used for bipolar II patients. 

To understand whether cognitive function and mood disorders are cooperatively influenced by genetic factors in AD and to know the potential impact that conventional neuroprotection can exert on mood disorders, we studied the effect of the therapeutic CNLA protocol on anxiety in AD and the differential APOE- and ACE-related responses distinguishing the influence of monogenic and bigenic variants on emotional conditions. 

Bupropion is also effective both in the treatment of depression and in smoking cessation. For more information, refer to Chapter 3 (Mood Disorders) and Chapter 6 (Substance Use Disorders). 

Depressed Mood. The preferred treatment for depression in a demented patient is an antidepressant of the SSRl or SNRl class. They are nsnally effective and reasonably well tolerated. When choosing an antidepressant, potential interactions with the many other medications that older patients are often taking mnst be considered. Please refer to Chapter 3 (Mood Disorders) for more information on potential drng interactions. 

Tryptophan depletion in healthy volunteers impairs the retrieval of learnt material (Park et al., 1994), an effect probably mediated through a selective impairment of episodic memory consolidation (Riedel et al., 1999 Schmitt et al., 2000). However, tryptophan depletion appears to have no effect on working memory (Riedel et al., 1999) and either no effect or an enhancement of tests of executive function (Park et al., 1994 Schmitt et al., 2000). Thus the abnormality in episodic memory in mood disorders could conceivably be related to an impairment in the 5-HT system, but such an impairment is unlikely to account for the abnormalities in working memory and executive function. Clearly then, changes in consciousness occurring in affective disorders are unlikely to be explainable on the basis of an abnormality in a single neurochemical system. 

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