PSYCHOPHARMACOLOGY

Hakan AtalayPsychiatrist

Yeditepe University Hospital

Curciculum Vitae

Place and Date of Birth: Ankara, 01.10.1964

Universirt: 1979-1985: Medical School of Ankara University

1986-1987: Compulsory Service at the Outpatient Service of the Ministry

of the National Education in Niğde1987-1991: Specialty Training at Bakırkőy Neuropsychiatric Hospital in IstanbulDissertation Thesis: Search for the Symptoms of Complex Partial Seizure in Patients with Bipolar Mood Disorder1992-1995: Psychiatrist at the Bakırkőy Neuropsychiatric Hospital 1995-1997: Psychiatrist at the Balıklı Rum Hastanesi 1998-2001: Psychiatrist at the Beyoğlu Research and Training Hospital2001-2005: Psychiatrist at the Haydarpaşa Numune Research and Training Hospital2005: Psychiatrist at the Psychiatry Department of Yeditepe University Hospital

HISTORY

1845 – Hashish intoxication 1869 – Clorale hydrate 1875 – Cocaine (Freud) 1882 – Paraldehyde 1892 – Research with morpine, ether, alcohol

and paraldehyde 1903 – Barbiturates 1917- Malaria fever therapy in psychosis

HISTORY

1922- Barbiturate induced coma 1927 – Insulin shock for sch 1931 – Reserpine for sch 1934 – Pentylentetrazole-induced convulsions 1936 – Frontal lobotomies 1938 – ECT 1940 – Phenitoin as anticonvulsant 1943 – LSD synthesized

HISTORY

1949 – Liyhium 1952 – Chlorpromazine 1955 – TCAs and MAOIs 1960 – Chlordiazepoxide

Classification

There has never been and still is not a consensus about how to classify psychotropic drugs. The terminology describing it is continually evolving.

As a rule, agents are organized according to structure (e.g., tricyclic), mechanism (e.g., MAOI), history (e.g., first generation, traditional), or uniqueness (e.g., atypical).

Classification

This lack of consistency in the classification of psychotropics causes confusion, but a more fundamental limitation is that drugs continue to be defined by their major indications.

For example, the standard categories of drugs are (1) antipsychotic drugs or neuroleptics used to treat psychosis, (2) antidepressant drugs used to treat depression, (3) antimanic drugs or mood stabilizers used to treat bipolar disorder, (4) antianxiety or anxiolytic drugs used to treat anxious states or used at higher doses, and (5) hypnotic agents to promote sleep.

Classification

Describing psychotropic drugs as diagnosis specific ignores the fact that, over time, most agents accumulate multiple therapeutic applications. For example, antidepressant drugs, in fact, have a wide spectrum of action. Agents such as the SSRIs and venlafaxine (Effexor), although still mainly used to treat depression, have also gained FDA approval as treatments for disorders as diverse as panic disorder, generalized anxiety disorder, social anxiety disorder, obsessive-compulsive disorder (OCD), posttraumatic stress disorder (PTSD), and premenstrual dysphoric disorder.

SSRIs

Fluoxetine (Prozac) Sertraline (Lustral) Citalopram (Cipram) Escitalopram (Cipralex) Paroxetine (Paxil) Fluvoxamine (Faverin)

Side-effects

GIS: * nausea * vomiting * anorexia * weight loss * dry moouth Sexual: * Lower libido

* Orgasmic difficulties Neuropsychiatric * Headache * Anxiety

TCAs

Amitryptiline (Laroxyl) Imipramine (Tofranil) Chlomipramine (Anafranil) Dothiepin

Maprotylin (Ludiomil) Mianserin (Tolvon) Opipramol (Insidon)

Side-effects

ANTICHOLINERGIC Dry mouth Blurred vision Constipation Urinary retention Drowsiness CARDIOVASCULAR Postural hypotension

Arrhytmias OVERDOSE Cardiotoxic Respiratory failure Seizures Coma

MAOIs

Irreversible: Phenelzine Isocarboxide Reversible: Moclobemide (Aurorix)

Side-effects

CARDIVASCULAR Postural hypotension Arrhytmias NEUROPSYCHIATRIC Drowsiness Insomnia Headache GI Increased appetite

Weight gain SEXUAL Anorgasmia HEPATIC Hepatotoxic

Serious side-effects

Hypertensive crisis (due to interactions between MAOIs and tyramine-containing compaouns)

5-HT syndrome (due to interactions between MAOIs and 5-HT-enhancing drugs)

(Less common with RIMAs)

Others:

NRI: Reboxetine (Edronax) SNRI: Venlafaxine (Efexor), Milnacipran (Ixel),

Duloxetine (Cymbalta) NDRI: Bupropion (Zyban) Mirtazapine (Remeron), Trazodone (Desyrel),

Thianeptine (Stablon: Selective Serotonine Reuptake Enhancer - SSRE)

Nor-adrenerjik Spesifik Serotonerjik Antidepresan (Mirtazapin)

ANTIPSYCHOTICS

TYPICALS - Phenothiazines (Chlorpromazine,

fluphenazine, thioridazine) - Butyrophenones (Haloperidol) Thioxanthine (Flupentixol) Benzamide (Sulpiride) ATYPICALS Clozapine, olanzapine, risperidone, quetiapine,

aripiprazole, sertindole, ziprasidone, paliperidone,...

Side-effects

EPS: Parkinsonism Acute dystonia Tardive dyskinesia Akathisia HYPERPROLACTINEMIA Impotence Amenorrhea

Side-effects

CHOLINERGIC BLOCKADE Dry mouth Blurred vision Urinary retension ALPHA ADRENERGIC BLOCKADE Postural hypotension HISTAMINERGIC BLOCKADE Sedation

NMS

Autonomic instability Hypertermia Raised creatinine phosphokinase Coma

Other side-effects

Cholestatic jaundice (phenothiazines) Photosensitivity Cardiac toxicity - arrhytmias (QT prolongation)

Side-effects with atypicals

Reduced propensity to EPS DM (All) Weight gain (All) Postural hypotension (All) Aganulocytosis (Clozapine) Hyperprolactinemia (Risperidone) Sedation (Olanzapine) QT prolongation (Ziprasidone)

ANXIOLYTICS

Long-acting: Diazepam (Diazem) Moderate: Alprazolam (Xanax) Lorazepam (Ativan) Short-acting: Triazolam (Halcion) Midazolam (Dormicum)

INDICATIONS

Anxiety Insomnia Alcohol withdrawal Status epilepticus Premedication

Side-effects

Drowsiness Dependence and tolerance Withdrawal syndrome CAUTION: * Respiratory depression * Hepatic impairment

Mood stabilisers

Lithium Sodium valproat Carbamazepine Lamotrigine

Lithium – side effects

Weight gain Fine tremor Muscle weakness Oedema Diarrhoea Nausea Vomiting Metallic taste

Nephrogenic DI Renal scarring Hypothyroidism Ca disturbance T-wave inversion Leucocytosis

Lithium contraindications

Pregnancy Renal disease Cardiac disease Addison's disease Untreated hypothyroidism

Sodium Valproate

Prevents GABA reuptake so enhances GABA-inhibitory transmission.

Reduces concentration of aspartate – an excitatory transmitter/

Blocks voltage-gated sodium channels/

Valproate side-effects

Nausea Vomiting Weight gain Rarely hepatic failure Pancreatitis Pancytopenia

Clozapine

Has a 3% risk of agranulocytosis. Any patient presenting with fever, sore throat or

infection requires FBC to check for neutropenia If neutropenic, immediately stop clozapine.

Lithium Toxicity

Low therapeutic index, so must be regularly monitored.

Severe nausea, vomiting, cerebellar signs, confusion, muscular twitching, spasticity, choreiform movements, convulsions, slurred speech, drowsiness, coma, death

Serum lithium level Stop lithium, give oral fluids, control convulsions

with diazepam, haemodialysis for severe poisoning

NMS

Hyperthermia, fluctuating level of consciousness, muscular rigidity, autonomic dysfunction with pallor, tachycardia, labile BP, sweating and urinary incontinence

Stop antipsychotic. Cardiovascular and respiratory support. Cooling. Bromocriptine may be used.

Usually lasts for 5-7 days and may require transfer to ITU.

20% mortality.