Biological Therapies د.ثراء الجودي

Biological therapies include: 1- Psycho-active medications (Psychopharmacology) 2- Electroconvulsive therapy (ECT) 3- Transcranial Magnetic Stimulation (TMS)

Psychopharmacology Medications are mainly categorized as: Antipsychotics Antidepressants Mood stabilizer Antianxiety and hypnotics (BZ and non-BZ) Other psycho-active agents

Psychopharmacology Antipsychotics Used to treat psychosis, e.g. schizophrenia, and depression with psychotic symptoms. Precise mechanism of antipsychotic action is unknown; however, they all block dopamine receptors. Some newer antipsychotic medications also block some serotonin receptors. The newer antipsychotics are more effective in treating the negative symptoms of schizophrenia.

Psychopharmacology Antipsychotic medications also block other kinds of receptors so they cause some side effects: cholinergic (causes side effects of dry mouth, blurred vision constipation, confusion , bradycardia & urine retention) histaminic (causes side effect of sedation and wt. gain) alpha-adrenergic receptors (causes side effect of postural hypotension and sexual side effects). All these side effects are more common in the old generation of medications.

Psychopharmacology The antipsychotics can be classified into 2 main groups: Typical (old, classical) Antipsychotics: Pure D2 antagonists. Include low-potency medications (like chlorpromazine) and high-potency antipsychotic medication (like haloperidol, and trifluperazine). These medications have more extrapyramidal symptoms.

Psychopharmacology Atypical (new): D1, D2, D4, 5HT2 antagonists: Clozapine, Olanzapine, reperidone, Queiapine (and others). The atypical drugs have less extrapyramidal side effects. The atypical antipsychotics are now regarded as the first choice treatment of any psychotic episode.

Psychopharmacology Typical Atypical Older agents Newer agents Dopamine effects Dopamine and serotonin effects Many side effects Fewer side effects Treat positive symptoms Treat positive and negative symptoms

Psychopharmacology GENERAL ADVERSE EFFECTS OF ANTIPSYCHOTIC MEDICATION Non Neurological Side Effects: Sedation: due to antihistamine activity. Hypotension: effect is due to alpha-adrenergic blockade and is most common with low-potency APMs (e.g. chlorpromazine). Anticholinergic symptoms: dry mouth, blurred vision (CI in some kinds of glaucoma), urinary hesitancy (CI in old age male with prostatic hypertrophy), constipation, bradycardia, and confusion (=delirium). Endocrine effects: gynecomastia, galactorrhhea, and amenorrhea due to blockade of Tuberoinfundibular tract. Dermal and ocular syndromes: photosensitivity, abnormal pigmentation, cataracts, retinitis pigmentosa (esp. with thioridazine). Other effects: agranulocytosis (with clozapine occur in less than 1% but is a dangerous side effect)

Psychopharmacology Neurological Side Effects (extra-pyramidal side effects, anti- psychotic induced movement disorders): These are caused by antagonism of dopamine D2 receptors, they are caused most commonly by typical antipsychotics. These include: ACTUE DYSTONIA BRADYKINESIA (PARKINSONISM) AKATHISIA TARDIVE DYSKINESIA (TD) NEUROLEPTIC MALIGNANT SYNDROME

Psychopharmacology ACTUE DYSTONIA: spasms of various muscle groups, typically occuring within hours to days (eg. torticolis= spasm in neck muscles, or oculogyric crisis= the eyes roll up and they cannot get them down,etc..). These Can be frightening to patient Treatment: use of anticholinergic medication such as procyclidine, or diphenhydramine. Benzodiazepines are also of help.

Psychopharmacology BRADYKINESIA (PARKINSONISM): slowed volitional movement, increased muscle tone, and resting tremor. Occur within weeks of treatment. AKATHISIA: motor restlessness. Takes week to develop. Often mistaken for anxiety and agitation. Treatment: switching to an antipsychotic medication with fewer extrapyramidal side effects (switch to new atypical drugs), and/or decreasing the dosage of antipsychotic medication and/or adding a beta-blocker or benzodiazepine.

Psychopharmacology TARDIVE DYSKINESIA (TD): Characterized by choreoathetosis and other involuntary movements. Movements often occur first in the tongue or fingers and later involve the trunk. Treatment: use newer antipsychotic medications(esp. Clozapine) NEUROLEPTIC MALIGNANT SYNDROME: rare and potentially life-threatening condition characterized by muscular rigidity, hyperthermia, autonomic instability, and delirium. Usually associated with high dosages of high-potency antipsychotic medication.CPK is usually diagnostic. Treatment: immediate discontinuation of medication and physiologic supportive measures; dantrolene or bromocriptine may be used.

Psychopharmacology ANTIDEPRESSANT MEDICATIONS Used to treat depression but also: various anxiety disorders, bulimia nervosa, enuresis, and chronic pain. All antidepressants increase serotonin and/or norepinephrine in the synapse. All antidepressants take about 3-6 weeks to work and all have equal efficacy. SSRIs are the first-line due to their lesser side effects. TCAs, and MAOIs (MonoAmine Oxidase Inhibitors) are less used. Some (esp. TCAs) blocks acetylcholine (muscarinic) and alpha-adrenernergic and histamine receptors. TCAs are dangerous in overdose. MAOIs can cause hypertensive crisis when taken with some food.

Psychopharmacology Examples of TCAs: amitriptyline, imipramine, and clomipramine. Examples of SSRIs: Fluoxetine, paroxetine, sertraline, fluvoxamine, citalopram and escitalopram. SSRIs have less number of serious side effects, few cardiac effects, few anticholinergic effect, and few hypotensive effects. Significant incidence of agitation, appetite loss, nausea, vomiting, headache, diarrhea, and sexual dysfunction.

Psychopharmacology Other, New Antidepressants Trazodone: markedly sedating, minimal anticholinergic effects, often used to treat depressed patients who have severe insomnia. Nefazodone: sedation similar to trazodone, but less sexual dysfunction the SSRIs or trazodone. Bupropion: activating, minimal hypotension, minimal cardiac effects, minimal sexual dysfunction; more likelihood of seizures. Venlafaxine: profile similar to SSRIs. Approved for use in Generalized Anxiety Disorder (GAD). Mirtazapine: profile similar to TCAs. Possibly more rapid onset of antidepressant effect than with SSRIs. Duloxetine: profile similar to SSRIs but approved for treatment of neuropathic pain and depression.

Psychopharmacology MOOD STABILIZING MEDICATIONS LITHIUM: Indications of lithium: • Bipolar and schizoaffective disorders: first –line medication for treatment and prophylaxis of mood episodes. • Adjunctive treatment of major depressive disorder: may augment responsiveness to antidepressant medications in some patients.

Psychopharmacology Sodium Valproate ( valproic acid) Treatment of choice for rapid-cycling bipolar disorder; or when lithium is ineffective, impractical, or contraindicated. Can be used as acute and maintenance treatment of manic episodes. Side effects: sedation, hepatotoxicity, wt. gain, hair fall and possible teratogenicity (spina bifida) CARBAMAZEPINE Second-line choice for treatment of bipolar disorder when lithium and Valproate are ineffective or contraindicated. Rare but serious hematologic and hepatic side effects and significant sedation make carbamazepine less useful.

Psychopharmacology Antianxity agents: Benzodiazepines (BZs): they activate GABA receptor. Tolerance and dependence may occur. E.g. diazepam, lorazepam, alprazolam, clonazepam, nitrazepam, and chlordiazepoxide. The antagonist at BZ receptor (anti-dote of BZs) is Flumazenil. Non-BZ antianxiety and hypnotics: Buspirone (non-sedating) and Zolpidem which is a hypnotic.

ELECTROCONVULSIVE THERAPY (ECT) Indications: Major depressive episodes that have not responded to antidepressant medication or mood stabilizers Major depressive episodes with high risk for immediate suicide Major depressive episodes in patients with contraindications to using antidepressant medication Major depressive episode in patients who have responded well to ECT in the past

ELECTROCONVULSIVE THERAPY (ECT) Side effects: Transient memory disturbance; it increases in severity over the course of ECT, and then gradually resolves over several weeks. Complications of associated anesthesia and induced paralysis Transient increased intracranial pressure: therefore, the presence of space-occupying intracranial lesions requires extreme caution. No absolute contraindication.

Transcranial magnetic stimulation (TMS) TMS is a therapy in which an electric current is applied to the scalp to generate a magnetic field about 2 cm deep that stimulates cortical interneurons lying parallel to the brain surface. TMS has been approved by the FDA and appears to be useful in patients with major depressive disorder and obsessive–compulsive disorder.

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