Depression from antidepressants

Redrobe JP, Dumont Y, Fournier A, Quirion R (2002a) The neuropeptide Y (NPY) Y1 receptor subtype mediates NPY-induced antidepressant-like activity in the mouse forced swimming test. Neiuopsychopharmacology 26 615-624 Redrobe JP, Dmnont Y, Quirion R (2002b) Neiuopeptide Y (NPY) and depression From animal studies to the hmnan condition. Life Sci 71 2921-2937 Redrobe JP, Dmnont Y, Herzog H, Quirion R (2003) Neiuopeptide Y (NPY) Y2 receptors mediate behaviour in two animal models of anxiety evidence from Y 2 receptor knockout mice. Behav Brain Res 141 251-255... 

Because it can be difficult to distinguish a severe, apathetic depression from a patient with catatonic features, an augmenting antidepressant should be considered. These agents may also help a post-psychotic depression, suggesting the importance of identifying subgroups that might benefit from this approach. This combination is also much more effective than antidepressant monotherapy in depression with psychotic features (see also Chapter 6 and Chapter 7). 

Indications that there may be antidepressant synergy from dual 5HT-NE actions that correspond with these theoretical molecular events comes from studies in which venlafaxine has produced increased remission rates in major depressive disorders as compared with SSRIs. Increased remission rates with the TCAs over the SSRIs have also been reported and support the concept of dual action being more efficacious than SSRI action alone for remission of depression in some patients. 

This chapter reviews the evidence that could establish whether drugs believed to be antidepressants really are disease-specific treatments for depression. The following chapter will consider whether they have any effects that might be useful in depression from a drug-centred perspective. 

Is there a demonstrable pathological basis to depression from which the action of antidepressant drugs can be understood ... 

Early signs of tricyclic antidepressant toxicity are due to anticholinergic effects and include tachycardia, mydriasis, dry mouth, low-grade fever, diminished bowel sounds, CNS excitation, and delirium. More serious toxicity is manifested by coma, respiratory depression, seizures, and cardiovascular toxicity including conduction disturbances, hypotension, ventricular arrhythmias, and asystole. Seizures cause hyperthermia, rhabdomyolysis, and metabolic acidosis. Clinical deterioration can be rapid and catastrophic in patients with tricyclic antidepressant overdose. Death most often occurs due to dysrhythmia and circulatory collapse. The typical therapeutic dose of a tricyclic antidepressant is 2-4 mg kg day Doses of 15-20 mg kg are potentially lethal. Therapeutic drug levels for most tricyclic antidepressants range from 100 to... 

Many patents have been issued on the use of pyrogaUol derivatives as pharmaceuticals. PyrogaUol has been used extemaUy in the form of an ointment or a solution in the treatment of skin diseases, eg, psoriasis, ringworm, and lupus erythematosus. GaUamine triethiodide (16) is an important muscle relaxant in surgery it also is used in convulsive-shock therapy. Trimethoprim (2,4-diamino-5-(3,4,5-trimethoxybenzyl)pyrimidine) is an antimicrobial and is a component of Bactrin and Septra. Trimetazidine (l(2,3,4-trimethoxybenzyl)piperazine (Vastarel, Yosimilon) is used as a coronary vasodilator. l,2,3,4-Tetrahydro-6-methoxy-l-(3,4,5-trimethoxyphenyl)-9JT-pyrido[3,4- ]indole hydrochloride is useful as a tranquilizer (52) (see Hypnotics, sedatives, ANTICONVULSANTS, AND ANXIOLYTICS). Substituted indanones made from pyrogaUol trimethyl ether depress the central nervous system (CNS) (53). Tyrosine-and glycine(2,3,4-trihydroxybenzyl)hydrazides are characterized by antidepressant and anti-Parkinson activity (54). 

Antidepressant Drugs. Figure 1 Effects of stress as a model for depression and the reversal by the use of antidepressants. Multiple intracellular targets might be involved in the regulation of plasticity and resilience by antidepressants, which block extracellular transporters. Adapted from [1],... 

Antipsychotic medications are indicated in the treatment of acute and chronic psychotic disorders. These include schizophrenia, schizoaffective disorder, and manic states occurring as part of a bipolar disorder or schizoaffective disorder. The co-adminstration of antipsychotic medication with antidepressants has also been shown to increase the remission rate of severe depressive episodes that are accompanied by psychotic symptoms. Antipsychotic medications are frequently used in the management of agitation associated with delirium, dementia, and toxic effects of both prescribed medications (e.g. L-dopa used in Parkinson s disease) and illicit dtugs (e.g. cocaine, amphetamines, andPCP). They are also indicated in the management of tics that result from Gilles de la Tourette s syndrome, and widely used to control the motor and behavioural manifestations of Huntington s disease. 

Antidepressant drugs are used to manage depressive episodes such as major depression or depression accompanied by anxiety. These drugs may be used in conjunction with psychotherapy in severe depression. The SSRIs also are used to treat obsessive-compulsive disorders. The uses of individual antidepressants are given in the Summary Drug Table Antidepressants. Treatment is usually continued for 9 months after recovery from the first major depressive episode. If the patient, at a later date, experiences another major depressive episode, treatment is continued for 5 years, and with a third episode, treatment is continued indefinitely. 

Medications that have been used as treatment for anxiety and depression in the postwithdrawal state include antidepressants, benzodia2epines and other anxiolytics, antipsychotics, and lithium. In general, the indications for use of these medications in alcoholic patients are similar to those for use in nonalcoholic patients with psychiatric illness. However, following careful differential diagnosis, the choice of medications should take into account the increased potential for adverse effects when the medications are prescribed to alcoholic patients. For example, adverse effects can result from pharmacodynamic interactions with medical disorders commonly present in alcoholic patients, as well as from pharmacokinetic interactions with medications prescribed to treat these disorders (Sullivan and O Connor 2004). 

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