Samantha 38g Filmographie

NEW mood stabilizers in bipolar disorders

(second part)

Miguel Pérez-Camacho Duque

The schizoaffective disorder, included in the group of so-called " atypical psychosis," answered the asymptomatic group and both a patient's own psychopathology of schizophrenia and mood disorder mood.

in DSM III-R (1988), we first provide diagnostic criteria for this table, requiring the presence of acute symptoms of mania or depression and schizophrenia, and the existence of delusions and hallucinations for at least 2 weeks in the absence of affective symptoms. The DSM IV (1994) only brings changes, distinguishing, as does the DSM III-R, a subtype schizoaffective bipolar and other depressive. For its part, the ICD-10 (WHO, 1992) includes schizoaffective mixed subtype.

Regarding the age of onset, it is early in the tables in the schizo-affective disorders (unipolar and bipolar) and slightly Late in schizophrenia.

is often an association between life stressors and subsequent clinical episode schizoaffective and greater socio-cultural level in these patients than observed in schizophrenia. Angst maintains that the risk of suicide in patients with schizoaffective disorder (15%) is higher than schizophrenic patients (10% of the study by Caldwell and Gottesman, 1990). It

consider three types of tables:

1. Bipolar (more frequent in young adults and closer to the emotional side of the spectrum)
2. Depressive (more common in adults older and seemingly closer to schizophrenia)
3. And mixed that are more difficult to diagnose and that would correspond to what Leonhard called "cycloid psychosis anxious."

In schizoaffective disorder, bipolar type (esquizomanía ), in principle, there is a good response to therapy of type antimanic drugs, including lithium salts, classic antipsychotics (haloperidol, chlorpromazine), benzodiazepines (clonazepam ) and anticonvulsants (carbamazepine, valproic acid, gabapentin, lamotrigine), which are generally used in partnership.

Studies with atypical antipsychotics offer new hope for the future. The effect of low dose risperidone and half (less than 6mg/día) with mood stabilizers has been successful.

On the olanzapine, because of its mechanism of action, this drug appears to possess antidepressant-like properties and possibly antimanic. Few data are taken from other atypical antipsychotic sertindole type (retired prematurely from the market due to its effect of lengthening the QT interval of the electrocardiogram), amisulpiride, quetiapine or ziprasidone.

The bipolar type schizoaffective disorder (bipolar esquizodepresivo ), preferably selective serotonin reuptake of serotonin, norepinephrine, or both together with antipsychotic drugs and mood stabilizers appear to be more reasonable therapeutic opinion.

In the unipolar type schizoaffective disorder (unipolar esquizodepresivo), treatment of patients esquizodepresivo unipolar subtype is more controversial, whereas some authors discourage the use of antidepressants and in many cases only the symptoms improve with treatment antipsychotics.

Where mixed episodes, treatment is comparable to that used in mixed bipolar disorders, so that greater emphasis should in antipsychotic treatment and, more specifically, the use of clozapine and probably the newer atypical antipsychotics (risperidone, olanzapine, quetiapine, amisulpiride, ziprasidone) in association with standard mood stabilizers.

As for the maintenance treatment , we encounter similar difficulties objectified for schizophrenia or bipolar disorders. After a first episode, in principle, maintain the treatment that has proved effective in the acute phase, at least for a year and a half, and indefinitely if we are faced with two or more episodes of the disease.

schizoaffective patients bipolar should be treated similarly to pure bipolar, so after a manic phase may be appropriate to reduce the doses of antipsychotics but without removing them completely and keep mood stabilizers. Since these patients (as well as bipolar) are at increased risk of extrapyramidal side effects before taking antipsychotic drugs should be administered in combination antiparkinsonian. In this sense, it is noted that the new atypical antipsychotics appears to be reduced substantially the risk of onset of tardive dyskinesia.

Regarding the mechanism of action of anticonvulsants in treating bipolar disorder, it has not yet been well established. They have different mechanisms of action, including the following:

• Modulation of gene expression through control of the enzyme protein kinase.
• Inhibition of the enzyme carbonic anhydrase.
• Action on ion channels (sodium, potassium, calcium) in the producing cell membarana neuronal voltage changes.
• Performance on second messenger enzyme inhibition on inositol monophosphatase involved in inositol fofatidil system, modulating the synthesis of protein G.
• Acting on the inhibitory neurotransmitter GABA, or by increasing its synthesis, release, inhibiting their metabolism or reuptake by GABA neurons.
• Performance in second messenger enzyme inhibition phosphokinase C.
• Reduced synthesis or release.

With the appearance in the clinic of the new antiepileptic opens a door of hope to this, above all, the future treatment of bipolar affective disorder and schizoaffective disorder probably due to its good tolerance, safety, profile interactions and their relative lack of serious adverse effects.

Among the new anticonvulsants, lamotrigine outside are the following:
Gabapentin
: This is a structural analogue of GABA. Its mechanism of action is complex and currently unknown, although it points to a reversal of the neuronal GABA transporter, thereby increasing the latter extracellularly. Something similar happens with the effective dose, for which there is a wide range (600-3600 mg / day), recommended for use by installment.

Its main adverse effects include sedation, ataxia, dizziness and gastrointestinal upset. Other less common side effects are headache, weight gain, nystagmus, diplopia, and tremor. Among its main interactions include antacids oral phenytoin.

It appears from several studies carried out, gabapentin possesses anxiolytic and antimanic effect, either alone or preferably in combination with other mood stabilizers. It also has some antidepressant effect and derivative thereof, a risk of inducing hypomanic desocmpensaciones. Its main clinical utility appears in social phobia and anxiety disorder, bipolar depression and dysphoric mania and refractory. Also you may have a useful role in treating disorders of impulse control.

Topiramate: Its mechanism of action derived from glutamatergic receptor blockade. Power, therefore, the action of GABA. It also acts as a calcium antagonist and inhibits the enzyme carbonic anhydrase. The optimal dose to achieve, in ascending and progressive, is 200-400 mg / day.

Side effects include sedation, numbness, gastrointestinal distress, difficulties in concentration, Memoir and verbal fluency and kidney stones. One of its main advantages is that unlike other drugs does not increase (even decreased) body weight by a mechanism of action remains desonocido. Presents a small number of interactions, including which include carbamazepine and phenytoin decrease the values \u200b\u200bof topiramate Induction your metabolism, and conversely decreases topiramate plasma levels of digoxin and oral contraceptives.
Topiramate has an antimanic effect in the acute phase, either as monotherapy or in combination and also in the acute phase antidepressant. Its main clinical utility found in refractory mania and dysphoric mania. Oxcarbazepine

: Presents a structure and a clinical profile similar to that of the carbmacepina, but with fewer side effects. The starting dose is 600 mg weekly. The therapeutic range is between 600-2400 mg / day.
Among its advantages are you do not have the toxic metabolites and present few drug interactions. The carbmacepina, phenytoin, phenobarbital and valproic acid plasma concentrations and reduce their vouchers, in turn, decreases the values \u200b\u200boxcabacepina oral contraceptives. The main adverse effects are nausea, vomiting, diarrhea and abdominal pain. Other less common side are sedation, drowsiness, headache, difficulty in concentration, amnesic disorders, dermatological disorders, increase in transaminases and alkaline phosphatase and hyponatremia, among others.

Its main use is in particular epilepsy and partial seizures with or without secondarily generalized tonic-clonic seizures. Although the effect has been attributed antimanic, its possible role in bipolar affective disorder and schizoaffective disorder, from the point of view, mood stabilizer, is to be determined. Tiagabine

: although its efficacy in manic phase seems doubtful, could tiagbina resultr ocmo HERAPY useful adjunctive bipolar I and schizoaffective disorder refractory. However, further studies are needed to support its therapeutic potential in these disorders. In Spain there is little use, like the three below.
Zonisamide: This is an anticonvulsant structurally similar to serotonin and a clinical profile similar to carbamazepine, with possible antimanic and mood stabilizer efficacy maintenance therapy.

levetiracetam and pregabalin : missing data regarding their role in bipolar disorder or schizoaffective.

Among the group of new antiepileptic drugs used in the treatment of bipolar disorder and schizoaffective disorder, lamotrigine is the one that seems to have a greater number of controlled clinical data supporting its efficacy, especially in bipolar depression in fast and cicladotes in bipolar disorder type II.

The mechanism of action of lamotrigine , although it is still unknown in many respects, it seems will guide through the blockade of serotonin 5HT3 and presynaptic inhibition of glutamate release.

Different studies seem to show that this drug could be useful not only in the stabilization of manic and / or mixed (including cicladotes fast) but also in the treatment of bipolar and unipolar depression. In fact lamotrigine seems to have a regulatory role of monoamine reuptake and especially serotonin, which can become clinically translated into an increase in serotonergic neurotransmission. Among

spontaneous reports of clinical cases, in which the association of lamotrigine in bipolar patients previously treated with other anticonvulsants (Lithium salts, valproate, carbamazepine) was satisfactory for clinical improvement and reduction in side effects attributable to drug treatment, notably with Walden (1996), Weisler (1994), Calíbrese (1996) , Labatte (1997), Maxoutova (1997) and Kotler (1998), among others.

found that, in general, describes an improvement in patients Bipolars type I and II, both as being manic depressive, hypomanic or mixed episode during and in rapid cyclers using lamotrigine as monotherapy or associated to other drugs, mood stabilizers, antipsychotics, benzodiazepines). To this effect should review the work of Calíbrese (2001 and 1999), Walden (2000), Fogelson (1997), Pinto (1997), Sport and Sachs (1997), as well as of Mandoki (1997), performed with bipolar children and adolescents, in which lamotrigine was associated with valproate. Work done

double-blind, placebo-controlled, in general we can say that lamotrigine has demonstrated clinical efficacy in the treatment of the following entities or processes:

bipolar depression, both studies short period of 7 weeks duration with lamotrigine as monotherapy in studies of one year follow up of bipolar type I and II. Lamotrigine is the only one of which used the new antiepileptic drugs has shown in clinical trials as authoritative a clear therapeutic potential in bipolar depression.

unipolar depression

affective disorders, both unipolar bipolar ocmo refractory to other drug treatments.
As prophylaxis maintenance monotherapy in bipolar rapid cycling.
As apparently effective treatment of mania.

Lamotrigine in pregnancy and lactation

Lamotrigine should not be used during pregnancy and / or breast, anus, be that in the opinion of the physician the potential benefit for use to the mother outweigh any possible risks to the developing fetus.

The data obtained so far removed from the registry and open by Glaxo-Wellcome laboratories purpose (Lamotriguine Pregnancy Registry) can say that:

At present there is no experience on the effect of lamotrigine on human fertility.

Lamotrigine is a weak inhibitor of the enzyme dihydrofolate reductase, and in this sense, it could have some teratogenic potential. The experience gained in the proportion of children born with birth defects after exposure to lamotrigine during the first trimester of pregnancy is no different to that provided to women affected by epilepsy undergoing anticonvulsant treatment.

Lamotrigine passes into breast milk during lactation at a rate of 40-60% in serum. In this sense, it seems advisable in these patients pose an artificial feeding.

Dosage and concomitant

In adult patients the mean daily dose of lamotrigine recomdada is between 100 and 400 mg / day at the beginning of treatment and then tapering down to a maintenance dose of 200 mg / day.

escalation is recommended before treatment to minimize's the risk of rash, the major side effect attributable to the drug.

lamotrigine monotherapy: 25 mg / day dose the first 2 weeks, 50 mg / day dose of Weeks 3 and 4 from there, increases between 59 and 100 mg every 1-2 weeks until dose maintenance.
This guideline also recommended that lamotrigine is combined with other drugs such as lithium and clonazepam. Lamotrigine

+ Valproate, 12.5 mg / day dose the first 2 weeks, 25 mg / day dose weeks 3 and 4, increases between 25 and 50 every 1-2 weeks until the maintenance dose and then decrease valproate. Lamotrigine + anticomicales

enzyme inducers: 50 mg / day dose the first 2 weeks, 100 mg / day dose of Weeks 3 and 4 from there, increments of 100 mg every 1-2 weeks until dose maintenance.

side effects

Major side effects associated with the clinical use of lamotrigine include skin rash maculopapular, apparently closely related to the initial drug dose administered, with the speed in climbing therapeutics, with the concomitant use of valproate (increases the mean half-life of lamotrigine) or sun exposure. In this case, should remain vigilant, because in a small per cent (less than 1%) of them could see a Steven-Johnson syndrome or toxic epidermal necrolysis.

Other less common side effects are: fatigue, headache, nausea, pain and itching. They have also been isolated reports of neutropenia and agranulocyte.

Lamotrigine has not gone directly related to increased concentrations hepatic transaminases and a incremetno in the final weight of the individual. If you have to come to an eventual withdrawal of the drug, recommended phasing in a period of not less than 1-2 weeks before stopping it completely.

Drug Interactions

Among the drugs that produce an induction of lamotrigine metabolism by decreasing their serum, and thus are clinical efficacy of carbamazepine, phenytoin, primidone, phenobarbital and acetaminophen.

By contrast, drugs such as sertraline or valproic acid inhibits lamotrigine metabolism, increase their plasma and thereby promote a greater presence of side effects and a consequent risk of poisoning by this drug. Conclusions



With the release of new antiepileptic drugs (lamotrigine, gabapertina, topiramate, oxcarbazepine, etc). , As has happened before in other areas such as psychosis or depression, it opens a wide range of possibilities for the treatment of bipolar and schizoaffective patients both in the search for a prophylactic effect on recurrence of each disorder in question as address when and to minimize both manic and depressive symptoms in the acute phase and monitor those patients resistant to conventional therapies. Bibliography



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