Neuroleptics depression from

Adverse effects Large doses of meperidine cause tremors, muscle twitches, and rarely, convulsions. The drug differs from opioids in that in large doses it dilates the pupil and causes hyperactive reflexes. Severe hypotension can occur when the drug is administered postoperatively. When used with major neuroleptics, depression is greatly enhanced. Administration to patients taking monoamine oxidase inhibitors (see p. 123) can provoke severe reactions such as convulsions and hyperthermia. Meperidine can cause dependence, and can substitute for morphine or heroin in use by addicts. Cross-tolerance with the other opioids occurs. 

This behavioural syndrome, rather emotively called learned helplessness", is widely believed to share many features of depression, not least because both culminate in psychomotor retardation and both are linked with experience of uncontrollable, unpredictable stress. Whether or not learned helplessness really is an analogue of depression remains controversial (Maier 1993). Nevertheless, escape deficits in rats are prevented by pretreatment with antidepressants from different generic groups. Other psychotropic agents, such as CNS stimulants and neuroleptics, are generally ineffective. 

The tricyclic antidepressants (TCAs) derive their name from their three-ringed molecular structure (Fig. 20.3) and emerged, in 1958, from a search for better neuroleptics than chlopromazine among the phenothiazines. The prototype, imipramine, turned out to be ineffective in treating the positive symptoms experienced by schizophrenics but it did relieve their depression (negative symptoms). In fact, imipramine is still the standard agent against which novel antidepressants are compared in clinical trials. 

Non-compliance issues appear more prevalent in some non-Western cultures. One study in South Africa revealed non-compliance rates to oral neuroleptics in two-thirds of Black patients and one-half of colored patients compared to only one-quarter of Caucasians (Gillis.Trollip, Jakoet etal., 1987). Cultural and communication factors were considered to be significant barriers apart from those related to cost and social factors. Kinzie et al. (1987) reported that despite prescribing adequate doses of tricyclic antidepressants (TCAs) to depressed Asian refugees,... 

Adverse effects of the TCAs on the brain include confusion, impaired memory and cognition and occasionally delirium some of these effects have been reported to occur in up to 30% of patients over the age of 50. These effects may occasionally be confused with a recurrence of the s)nnptoms of depression and are probably due to the central antimuscarinic activity of these drugs. Tremor also occurs frequently, particularly in the elderly, and may be controlled by the concurrent administration of propranolol. Neuroleptics are normally not recommended to be used in combination with TCAs as they are liable to accentuate the side effects of the latter drugs. The risk of seizures, and the switch from depression to mania in bipolar patients, has also been reported following TCA administration. 

Some neuroleptic agents, like cycloindole (497), which has a modified tryptamine structure, and flucindole (498), a difluoro analog of cycloindole, have found use in therapy because of their anti-depressant and anti-psychotic activity (463,464) (Scheme 4.11). 3-Chlorocarbazole (385) (see Scheme 2.102), isolated from female bovine urine, has Diazepam-like activity (354). 

These are usually treated with sedative neuroleptics (as for schizophrenia, above). Treatment must also aim to support the patient socially including for instance advising on legal protection from the financial or other consequences of mania. One of the risks of treatment is the sudden mood swing at the end of the manic episode, with acute depression possibly triggered by the neuroleptics. Because of the concern for the manic episode and symptoms, return to normal is viewed with relief, and the downswing may go un-noticed, with the concomitant suicidal risk. 

The primary indication for ECT in adolescents is the short-term treatment of mood symptoms, depressive or manic (Walter et al., 1999). Mood symptoms in the course of major depression, psychotic depression, bipolar disorder, organic mood disorders, schizophrenia, and schizoaffective disorder respond well to ECT. Psychotic symptoms in mood disorders also respond well to ECT whereas the effectiveness of ECT in the treatment of psychotic symptoms in schizophrenia is doubtful. There are suggestions that other uncommon clinical conditions in adolescents such as catatonia and neuroleptic malignant syndrome also benefit from ECT. The effectiveness of ECT seems to lessen when there is a comorbid personality disorder or drug and/or alcohol problems. There are very few data about usefulness on prepubertal children. 

Despite this favorable result, lithium was hardly considered as a psychopharmaceutical for many years. There were a variety of reasons for this. Firstly, mania is not a very common psychosis and there is spontaneous remission in many cases. There were thus not so many occasions where lithium treatment was indicated. Secondly, lithium salts were considered to be toxic because for some time they had been given in excessive doses to patients with heart failure and in this way, had led to a number of fatalities (Cade, 1970). Thirdly, a few years after Cade s first publication psychiatrists attention had been claimed by chlorpromazine and the subsequent neuroleptics and antidepressants, thus explaining why lithium almost fell into oblivion. It was onl> in the 1960s that it once more attracted some interest, after the Danish psychiatrist Mogens Schou had shown that lithium salts were not only useful in the manic phase of manic depressive illness but also could prevent depressive episodes in patients suffering from bipolar psychoses. 

Small andKellams (1974) noted reports of patients becoming suicidal as a result of treatment with the long-acting injectable form of Prolixin. Others have confirmed that suicide can result from neuroleptic-induced depression (Alarcon et al., 1969 Hogan et al., 1983). 

In regard to neuroleptics, we found that pioneers in their use were most straightforward about its brain-disabling effects. We find the same phenomenon with lithium. Cade (1949) indicated that lithium, when used for other medicinal purposes, produced actual mental depression in a variety of patients, not just those suffering from mania or manic depression. The drug enforced a so-called quieting effect on persons he considered schizophrenic (dementia praecox, in his nosology) ... 

During withdrawal from both the older and newer neuroleptics, the individual can experience severe abnormal movements during withdrawal. They can be painful and frightening and can become persistent in the form of tardive dyskinesia (chapter 4). Severe emotional suffering and psychosis are common withdrawal reactions (chapters 4 and 5). Children may undergo severe behavioral worsening. Depression can occur. 

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