Monday, 24 June 2013

Antipsychotics and why I am pleased to not be on them

Oh how I do not envy Schizophrenics that live in the US and other countries without an equivalent to the Australian Public Benefits Scheme (PBS) and are without health insurance... all of the antipsychotics that they are almost obliged to take because if they do not they will likely end up institutionalised, usually cost between $10 (which, albeit, is not too much) and $1,000 per month and if that is not bad enough the disease itself and the drug's side effects can make it difficult for schizophrenics to get a job and hold them done when they do get them. Nearly all antipsychotics have side effects that can be disabling, especially in the first few weeks of treatment. The most disabling of these side effects are the extrapyramidal side effects (EPS) which are side effects associated with one’s voluntary movements such as tremor, difficulty initiating and stopping one's voluntary movements, EPS can include people experiencing involuntary movements such as tics. Overall the EPS are practically indistinguishable from the symptoms of Parkinson's disease.1

Fortunately, however, since the 1990s and the advent of the second-generation antipsychotics (atypical antipsychotics) these extrapyramidal side effects have become increasingly rare and usually when they do occur they are only temporary, but despite this these newer drugs do have their dangers and side effects that can interfere with work.

Their dangers include their potential for causing weight gain, metabolic syndrome (which is a combination of things that can be linked to metabolic problems such as raised blood triglycerides, reduced blood levels of "good cholesterol" (HDL), increased blood pressure, and reduced ability to utilise glucose), cardiovascular disease (heart disease and blood clots, e.g. deep vein thrombosis), in the case of clozapine rare blood disorders such as agranulocytosis (a drastic drop in white blood cell count, leaving patients wide open to often life-threatening infections), increased risk of life-threatening, often random problems with heart rhythm (particularly ziprasidone), neuroleptic malignant syndrome (NMS; see neuroleptic malignant syndrome for details) and tardive dyskinesia (TD; a more treatment-resistant [i.e. it usually does not seem to respond much at all to dose reductions or even cessation of antipsychotic treatment] form of EPS). Many of these drugs also have, a sometimes severe degree of drowsiness as a potential side effect during the first few days of treatment (particularly clozapine, quetiapine and olanzapine have a tendency for causing these kind of side effects) and postural hypotension (also known as dizzy spells; defined as a significant drop in blood pressure upon standing up). The older antipsychotics such as haloperidol and the newer antipsychotic risperidone also have a high propensity for causing a side effect called hyperprolactinaemia which can be both embarrassing and problematic. By embarrassing I mean hyperprolactinaemia can cause men and non-pregnant/breast-feeding women to lactate. The problematic side effects that normally occur with chronic (long-term, in this case over the course of weeks or more) hyperprolactinaemia include sexual dysfunction, infertility, increased risk of breast cancer and osteoporosis (reduced bone mineral density, i.e. brittle bones).1-4

Table 1: Comparative Side Effects, Costing and Dosing of Antipsychotics1-7
Name
Costing & Dosing
 Comparative Side Effect Liabilitya
Drug
BN
TDR
MiMD
MaMD
ASE
HPE
EPS
PH
SE
W
MS

Typical Antipsychotic
Chlorpromazine
THORAZINE
150-800
$18.00
$64.80
+++
++
++
+++
+++
+++
+++

Fluphenazine
PROLIXIN
1-30
$6.90
$30.60
+/-
+++
+++
++
++
+/-
+/-

Haloperidol
HALDOL
2-20
$5.70
$16.20
-
+++
+++
++
+/-
-
-

Loxapine
LOXITANE
15-60
$21.30
$35.40
++
++
++
++
+++
++
++

Perphenazine
TRILAFON
12-64
$18.00
$25.20
+
+++
++
++
++
+
+

Trifluoperazine
STELAZINE
4-40
$19.80
$45.00
+
+++
++
+
++
+
+

Atypical Antipsychotic
Aripiprazole
ABILIFY
5-30
$105.90
$167.10
+/-
-
+/-
++
+/-
+
+/-
Asenapineb
SAPHRIS
10-20
$45.60
$52.20
-
-
+
++
++
+
+
Clozapine
CLOZARIL
200-900
$74.40
$334.80
++
-
-
+++
+++
+++
+++
Iloperidoneb
FANAPT
2-24
$52.20
$277.20
+/-
-
+/-
+++
++
++
+
Lurasidoneb
LATUDA
40-160
$158.70
$696.30
-
-
+
-
-
-
-
Olanzapine
ZYPREXA
5-30
$12.90
$24.90
++
-
+
+
+++
+++
+++
Paliperidoneb
INVEGA
3-15
$59.70
$216.90
-
-
+
++
++
+
+
Quetiapine
SEROQUEL
50-800
$13.20
$60.00
++
-
+
+++
++
++
++
Risperidone
RISPERDAL
2-8
$6.00
$18.60
-
+++
++
++
+
++
++
Ziprasidone
GEODON
40-160
$21.60
$50.40
-
++
+
++
+
+
+

TDR: Typical daily oral/sublingual (under the tongue) dosage range in mg/day for adults with schizophrenia. MiMD: Min Price (USD) per month (30 days) for the lowest typical daily dose, according to Pharmacy Checker. MaMD: Min price (USD) per month (30 days) for the maximum typical daily dose, according to Pharmacy Checker.

ASE: Anticholinergic side effects which are side effects that affect the involuntary movements of the body such as those of the GI tract, eyes, etc. Examples include dizziness, blurry vision, dry mouth, constipation, etc. HPE: Hyperprolactinaemia. EPS: Extrapyramidal side effects. MS: Metabolic side effects. PH: Postural hypotension. SE: Sedation.

+++ means that the side effect is severe, ++ means the side effect is moderately severe, + means the side effect is mild in severity, and – means the side effect is rare or just does not occur. +/- indicates that it is uncertain whether the side effect exists but if it does it is mild.

a— the severity is approximated using a number of things, including the literature (1-4) and the pharmacodynamics of the drug in question.
b— these agents are so new that there simply is not enough clinical data to truly know how prone they are to causing side effects and hence their pharmacodynamic profile is being used to estimate their side effect liability.

Antipsychotics are also sometimes used to treat other conditions such as bipolar disorder, autism, major depressive disorder (MDD; clinical or unipolar depression), dysthymia (a mild chronic depression), personality disorders and anxiety disorders. In bipolar disorder and major depressive disorder they are normally used to treat patients with psychotic features (e.g. hallucinations, delusions, etc.), however in some cases, particularly treatment-resistant cases, it is used in the treatment of patients without psychotic features. They also have some anxiolytic (anti-anxiety) properties and hence can be helpful in anxiety disorders and major depressive disorder with anxious features (some people with MDD suffer anxiety with their condition).

Another thing about antipsychotics is that they very rarely manage to eliminate all of a patient's symptoms. Antipsychotics normally just tackle the positive symptoms of schizophrenia (hallucinations, delusionsthought and movement problems) while having limited effects on the negative (blunted ability to express and even experience emotions, trouble feeling pleasure, speech problems, lack of motivation) and cognitive symptoms of schizophrenia (working memory, problem solving, social intelligence and processing speed impairments). The atypical antipsychotics tend to have a greater impact on the negative symptoms of schizophrenia than their typical counterparts, and there is evidence to suggest that asenapine and lurasidone might have a greater impact on the negative and cognitive symptoms of schizophrenia than other antipsychotics. Some people on antipsychotics (according to a psychologist I was once seeing, quite a few) still have some residual hallucinations that can, hopefully, be managed with the help of psychotherapy (usually a mind over matter thing, working with a psychologist/psychiatrist on ways to ignore the hallucinations).1-4 

Glossary

Pharmacodynamics: How drugs interact with their molecular targets (i.e. receptors, enzymes, etc.).

Reference List

1.       Brunton LL, Chabner B, Knollman B. Goodman & Gilman’s The Pharmacological Basis of Therapeutics. 12th Ed. New York, NY: McGraw-Hill Medical; 2011. p. 417-451.
2.       Stein DJ, Kupfer DJ, Schatzberg, American Psychiatric Publishing. The American Psychiatric Publishing Textbook of Mood Disorders. Washington, DC: American Psychiatric Pub.; 2005. p. 291-301.
3.       Truven Health Analytics, Inc. DRUGDEX® System (Internet) [cited 2013 Jun 25]. Greenwood Village, CO: Thomsen Healthcare; 2013.
4.       Davis KL, Charney D, Coyle JT, Nemeroff C, American College of Neuropsychopharmacology. Neuropsychopharmacology: The Fifth Generation of Progress: An Official Publication of the American College of Neuropsychopharmacology. Philadelphia, PA: Lippincott Williams & Wilkins; 2002. p. 775-781.
5.       Komossa K, Depping AM, Gaudchau A, Kissling W, Leucht S. Second-generation antipsychotics for major depressive disorder and dysthymia. Cochrane Database of Systematic Reviews [Internet]. John Wiley & Sons, Ltd; 2012 [cited 2013 Jun 25]. Available from: http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD008121.pub2/pdf.
6.       Depping AM, Komossa K, Kissling W, Leucht S. Second-generation antipsychotics for anxiety disorders. Cochrane Database of Systematic Reviews [Internet]. John Wiley & Sons, Ltd; 2011 [cited 2013 Jun 25]. Available from: http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD008120.pub2/pdf.
7.       Komossa K, Depping AM, Meyer M, Kissling W, Leucht S. Second-generation antipsychotics for obsessive compulsive disorder. Cochrane Database of Systematic Reviews [Internet]. John Wiley & Sons, Ltd; 2010 [cited 2013 Jun 25]. Available from: http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD008141.pub2/pdf

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