History

Fact Explanation
Introduction to the disease Huntington Chorea also called as Huntington’s disease is a progressive disorder of motor, cognitive, and psychiatric disturbances. It is an adult onset autosomal dominant inherited condition which has mean age of onset around 35 to 44 years. And the other form called juvenile HD has an age of onset before 20 years of age. Prior to onset and diagnosis, individuals who have a Huntington disease-causing allele are appear healthy and free of detectable clinical signs or symptoms. Preclinically however they may have subtle and otherwise undetected changes in motor skills, cognition, and personality so called 'presymptomatic' phase.[1]. However the clinical diagnosis of HD established by the presence of chorea, psychiatric and/or cognitive signs and an autosomal dominant pattern of inheritance or family history.[3].
Chorea Both involuntary and voluntary movement disturbances occur. Chorea is an involuntary movement disorder. Non repetitive, non-periodic jerking is seen in face, limbs or trunk. It presents over 90% of individuals.[1]. It starts at the early stage of the disease involving distal extremities such as fingers and toes.[3].But in next stage that means middle stage chorea becomes more prominent. voluntary activities increasingly become difficult with twisting and writhing motions, jerks, staggering, swaying, disjointed gait which can seem like intoxication. It seems to be increasing during the first ten years. At late stage patient may present with severe chorea, but it is less common. Chorea found to be occur when patient awakes , increased with stress and it cannot voluntarily suppressed.[1].Facial choreatic movements can lead to a continuous movement of facial muscles. Eyebrow is lifted, an eye closed, the head is tends to bent or turned while the tongue is protruded with the lips pouting. Extension movements of the long back muscles are found to be more prominent.[3]. Disease will cause selective degeneration of neurons in the caudate and putamen. The neurobiologic basis for chorea is degeneration of medium spiny, enkephlin containing neurons of the indirect pathway of movement control in the basal ganglia.Substantia nigra, hippocampus, and various regions of the cortex also can get involved. [1].
Dysarthria and dysphagia Talking and swallowing gradually get affected. It may leads to recurrent choking attacks. Later on Dysarthria and dysphagia becomes more prominent and some patients may remain muted.[3].
Bradykinesia It means difficulty in initiating and continuing movements so called slowness of movements. It Occurs due to basal ganglia involvement. Seen in late stage of disease.[1],[3].
Akinesia Also resulted due to involvement of basal ganglia. Found in late stage of disease. It causes difficulty in starting movements.[3],[1].
Hypokinesia Hypokinesia, akinesia, and rigidity leading to a slower pace of all activities as well as severe hesitation in embarking on a movement. However the balance between chorea and hypokinesia is individually determined .[3].
Dystonia Another feature that occurs in middle stage of disease due to basal ganglia involvement.[1]. It is characterized by slowness of movements and an increased muscle tone. It will leads to abnormal posture such as torticollis, and also rotation of the trunk or limbs. Dystonia can be the first motor sign in Huntington's disease.[3].
Gait disturbances The presence of hyperkinesia and hypokinesia results in difficulties in walking and standing. It leads to an ataxic gait and frequent falls. Cerebellar signs may appear sometimes causing drunk' or 'cerebellar ataxia'-like walking which makes difficult to distinguish from choreatic walking.[3].
Depression Major depression is a common psychiatric diagnosis in HD. Disease itself has 30% to 40 % lifetime prevalence to develop depression. Severe cases may leads to delusions or auditory hallucinations. Depression in HD is found to be associated with reduced glucose metabolism in the orbitofrontal and inferior prefrontal regions.[2]. However the etiology of depression in HD is not very clear and it may believe to be a pathologic rather than a psychological consequence of having the disease.[1].
Increased suicide risk Suicides as well as suicidal ideas are common in persons with HD. The tendency to suicide increased in just prior to receiving a diagnosis and later, when patient experiences a loss of independence.[1]. Suicide rate is around 4 to 6 times that of the general population.[2].
Mania It has lifetime prevalence of 5% to 10% in HD. Bipolar syndrome also found to occur. They may present with features such as elevated or irritable mood, , increased activity, hypersexuality, impulsiveness, decreased need for sleep, and also a grandiose self-attitudes. Delusions and hallucinations are found in severe cases.As like major depression, mania can be the first manifestation of HD.[2].
Delusions They also have increased risk of having delusions. They are often paranoid delusions.[1].
Hallucination Found to be occurred in HD. But less common.[1]. Paranoid and acoustic hallucinations are associated with schizophrenia[3].
Schizophrenia Lifetime risk of having schizophrenia in HD patient is around 9%.[2].
OCD Found to be occur in HD. Classical cases of OCD exist in Huntington's disease. Frontal lobe, caudate, and globus pallidus have been found to be implicated in OCD.[2].
Apathy Behavioral disturbances such as apathy are commonly seen in HD. Often noticed by the family members rather than the patient. It is predictable symptom of HD, and not synonymous with depression.[2].
Irritability Irritability and aggression is another two associated symptoms.[2].Irritability is often the very first sign of HD.[3].
Delirium Commonly found in HD. Several factors may contribute to occurrence. They are volume depletion, poor nutrition, metabolic disturbances, medical complications as well as medication effects. A sudden change in behavior or a decline in cognitive abilities should be evaluate for delirium.[2].
Demoralization Patients with HD can become demoralized. This usually occurs at times of loss such as give up driving or forced to stop working.[2].
Sexual problems Hypoactive sexual desire and inhibited orgasm are the commonly encountered sexual problems. This may occur around 63% and 56% of men, and 75% and 42% of women. Sexual aberrations has also been reported.[2].
Sleep disturbances Patients may develop insomnia due to verity of reasons including depression, , deterioration of the sleep-wake cycle, involuntary movements and lack of daytime stimulation.[2]. Sleep cycles may disrupted as a result of hypothalamic dysfunction.[1].
Dementia Cognitive decline is an major manifestation of HD. Patients with HD lose the capability of distinguishing what is relevant and what can be ignored. Their cognitive and motor behaviors are not goal directed or planned.They lose flexibility of mind. So they no longer able to make mental adjustments. Misjudgments further lead to complicated situations.[3]. Memory impairment can be seen and however in early stage of the disease the memory impairment is found to be less severe than Alzheimer disease.[1].
Weight loss Unintended weight loss has been reported in all patients in early stage of disease. However there is no relationship between weight loss and chorea or other movement disorders. But decreased appetite, slower functioning, difficulty in handling food and swallowing may play a role. Simultaneously hypothalamic neuronal loss may also contribute.[3].
Profuse sweating It is a secondary symptom occurs due to autonomic disturbances.[3].
Family history of HD Since HD is inherited in an autosomal dominant manner family history plays an important role.[1].
References
  1. WARBY SC, GRAHAM RK, HAYDEN MR, PAGON RA, ADAM MP, ARDINGER HH, BIRD TD, DOLAN CR, FONG CT, SMITH RJH, STEPHENS K. Huntington Disease [online] 1993 [viewed 27 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/20301482
  2. ROSENBLATT A. Neuropsychiatry of Huntington's disease Dialogues Clin Neurosci [online] 2007 Jun, 9(2):191-197 [viewed 27 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3181855
  3. ROOS RAYMUND A.C.. Huntington's disease: a clinical review. Array [online] 2010 December [viewed 27 September 2014] Available from: doi:10.1186/1750-1172-5-40

Examination

Fact Explanation
Involuntary movements. General examination may shows involuntary, unwanted movements .The movements often occur in the distal extremities such as fingers and toes initially.Small facial muscles also can get involved.Gradually these movements found to be spread to all other muscles from distal to more proximal and axial.[3].
Higher function assessment findings Marked decreased in cognitive functions can be seen. Slowness of thought processes,forgetfulness, impaired visuospatial abilities, and impaired ability to manipulate acquired knowledge can be demonstrated. [1].However semantic memory found to be be spared to a certain extent.[3]. Lack of awareness may also seen.Language functions are relatively preserved but in late stage of disease, paraphasic errors,cortical speech abnormalities as well as word finding difficulties are commonly found.[1]. Several scoring systems has been used for assessment. "Huntington's Disease Rating Scale" is one of those, which consist of motor, behavior, cognitive and functional ,followed by a history and medication scheme.[3].
Abnormal eye movements Cranial nervous system examination reveals abnormal eye movements. Oculomotor disturbances occur early stage and found to be worsen progressively. Damage to the basal ganglia which play a major role in controlling eye movements causes variety of ocular disturbances such as difficulty in initiating ocular saccades, slow and hypometric saccades, and problems in gaze fixation. Those may be seen about 75% of symptomatic individuals.[1].
Rigidity Seen in late stage of disease due to basal ganglia involvement. Rigidity further causes slowness of movement and some old patients may bed-bound with rigidity and flexion contractures in the extremities at the late stage of disease.[1],[3].
Hyperreflexia Hyperreflexia occurs in early stage around 90% of individuals.[1].
Clonus Clonus and extensor plantar responses occur late stage of the disease and less frequently.[1].
Babinski sign Pyramidal signs such as Babinski sign is present incidentally.[3].
Psychiatric assessment findings Since the disease is associated with several Psychiatric manifestations psychiatric assessment should be carried out by a psychiatrists. It may able to detect Schizophrenia, depression, suicidal ideas, OCD,delusions , hallucinations etc... Neuropsychologic testing may also reveals impaired visuospatial abilities.[1].
References
  1. WARBY SC, GRAHAM RK, HAYDEN MR, PAGON RA, ADAM MP, ARDINGER HH, BIRD TD, DOLAN CR, FONG CT, SMITH RJH, STEPHENS K. Huntington Disease [online] 1993 [viewed 27 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/20301482
  2. ROSENBLATT A. Neuropsychiatry of Huntington's disease Dialogues Clin Neurosci [online] 2007 Jun, 9(2):191-197 [viewed 27 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3181855
  3. ROOS RAYMUND A.C.. Huntington's disease: a clinical review. Array [online] 2010 December [viewed 27 September 2014] Available from: doi:10.1186/1750-1172-5-40

Differential Diagnoses

Fact Explanation
Sydenham's chorea (SC) It is an autoimmune disease that occurs following a infection with group A beta hemolytic streptococci in children.Irregular, non stereotypedapid, involuntary movements that affect all limbs, face, and trunk are the classical presentation. Obsessive compulsive signs, emotional lability and attention difficulties also can occur.[1].
Thyrotoxicosis Thyrotoxicosis may also leads to abnormal movements such as chorea.[3]. Other features include weight loss, anxiety or nervousness, tremulousness, diarrhea, palpitations, muscular weakness,profuse sweating, and heat intolerance.They may also give a history of getting treatment for an"overactive" thyroid. Rare and highly dangerous form of thyrotoxicosis is called thyroid storm which may leads to extreme temperature elevation, change in mental status that ranging from extreme agitation to coma.[2].
Tardive dyskinesia It is potentially irreversible syndrome of involuntary hyperkinetic movements. It found to be occurs in patients who receiving extended neuroleptic (antipsychotic) drug therapy. Choreoathetoid dyskinesias in the orofacial, limb, and truncal regions are characteristic.Typical signs include chewing, vermicular tongue activity, tongue protrusion, lip smacking, puckering, and paroxysms of rapid eye blinking. Dyskinesias in the fingers may manifest as the individual is playing an invisible guitar or piano. Some may have tardive dystonia and tardive akathisia.[4].
Wilson disease It is a disorder of copper metabolism. Hepatic, neurologic, or psychiatric disturbances may occur.Recurrent jaundice is a manifestation of liver disease.Tremors, poor coordination, loss of fine-motor control, chorea and choreoathetosis like movement disorders occur as neurologic presentations. Some may have mask like face, rigidity, gait disturbance as well as pseudobulbar involvement. Depression, disorganization of personality, neurotic behaviors and intellectual deterioration are found to be occured due to psychiatric disturbances.[5].
Huntington disease-like 2 (HDL2) It causes progressive triad of movement, emotional, and cognitive abnormalities. Some patients it resembles juvenile-onset Huntington disease. they present with diminished coordination and weight loss. Rigidity, bradykinesia and tremor obtain in some individuals. Hyperreflexia and dysarthria are other two neurological manifestations.[6].
Chorea-acanthocytosis (ChAc) Progressive movement disorder, cognitive and behavior changes are characteristic. They may have myopathy which is sub clinical. Chorea is the main movement disorder but some individuals present with parkinsonism. Dystonia in tongue and oral region , cause dysarthria and serious dysphagia with resultant weight loss.More than half of the individuals may develop seizures.[7].
Parkinson's Disease (PD) It is one of the frequent neurodegenerative brain diseases. Disease starts at middle age with increasing prevalence above the age of 50 years.At least two of the three cardinal signs including bradykinesia, rigidity and tremors need for clinical diagnosis of PD.They get resting tremors. Other features include impaired postural reflexes, mask like face, low speech volume, difficulty in swallowing , micrographia,flexed posture, problem in initiating movements and small shuffling steps. They may also get depression.[8].
References
  1. GIMENO H, BARRY S, LIN JP, GORDON A. Functional Impact of Sydenham's Chorea: A Case Report Tremor Other Hyperkinet Mov (N Y) [online] :tre-03-128-3381-1 [viewed 27 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3607915
  2. MELISH JS, WALKER HK, HALL WD, HURST JW. Thyroid Disease [online] 1990 [viewed 27 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/21250085
  3. WARBY SC, GRAHAM RK, HAYDEN MR, PAGON RA, ADAM MP, ARDINGER HH, BIRD TD, DOLAN CR, FONG CT, SMITH RJH, STEPHENS K. Huntington Disease [online] 1993 [viewed 27 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/20301482
  4. CASEY DE. Tardive dyskinesia. West J Med [online] 1990 Nov, 153(5):535-541 [viewed 27 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1002605
  5. WEISS KH, PAGON RA, ADAM MP, ARDINGER HH, BIRD TD, DOLAN CR, FONG CT, SMITH RJH, STEPHENS K. Wilson Disease [online] 1993 [viewed 27 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/20301685
  6. MARGOLIS RL, PAGON RA, ADAM MP, ARDINGER HH, BIRD TD, DOLAN CR, FONG CT, SMITH RJH, STEPHENS K. Huntington Disease-Like 2 [online] 1993 [viewed 27 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/20301701
  7. VELAYOS BAEZA A, DOBSON-STONE C, RAMPOLDI L, BADER B, WALKER RH, DANEK A, MONACO AP, PAGON RA, ADAM MP, ARDINGER HH, BIRD TD, DOLAN CR, FONG CT, SMITH RJH, STEPHENS K. Chorea-Acanthocytosis [online] 1993 [viewed 27 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/20301561
  8. LEENDERS KL, OERTEL WH. Parkinson's Disease: Clinical Signs and Symptoms, Neural Mechanisms, Positron Emission Tomography, and Therapeutic Interventions Neural Plast [online] 2001, 8(1-2):99-110 [viewed 29 September 2014] Available from: doi:10.1155/NP.2001.99

Investigations - for Diagnosis

Fact Explanation
MRI Diagnosis based on clinical symptoms,sign and family history. They are usually sufficient for diagnosis.No imaging, general blood tests or other diagnostic tools are helpful.[1]. However MRI produce additional support for the clinical diagnosis. MRI scans can identify significant striatal atrophy as many as 11 years prior to clinical onset of the disease.Significant progressive volumetric loss of the striatum Is the most consistent change in the HD brain which has been detected by structural MRI. Functional MRI shows reduced task activation in several subcortical and cortical regions as well as increased activation in different cortical areas in patients with HD.[3].
CT and SPECT They also provide an additional support for the clinical diagnosis.Striatal atrophy and global changes can be detected in patients with HD even before the onset of symptoms.[2].
PET PET studies in HD gene carriers have shown severe involvement of the postsynaptic dopaminergic system. But the dopaminergic nerve terminals seem to be less affected.[3].
Molecular Genetic Testing HTT (HD) is the only gene found to be associated with Huntington disease.The only mutation observed in HD is trinucleotide CAG repeat expansion. Those are useful to establish diagnosis.[2].
Serum copper and ceruloplasmin levels Useful to exclude Wilson's disease. They will show low serum copper and ceruloplasmin concentrations. They may also show increased urinary copper excretion. Diagnosis of Wilson's disease established with the help of above biochemical tests and presence of Kayser-Fleisher rings in the cornea.[4].
Thyroid function tests Useful to exclude thyrotoxicosis. Elevated level of T3 and T4 with decreased TSH levels can be seen.[5].
References
  1. ROOS RAYMUND A.C.. Huntington's disease: a clinical review. Array [online] 2010 December [viewed 27 September 2014] Available from: doi:10.1186/1750-1172-5-40
  2. WARBY SC, GRAHAM RK, HAYDEN MR, PAGON RA, ADAM MP, ARDINGER HH, BIRD TD, DOLAN CR, FONG CT, SMITH RJH, STEPHENS K. Huntington Disease [online] 1993 [viewed 27 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/20301482
  3. NICCOLINI F, POLITIS M. Neuroimaging in Huntington's disease World J Radiol [online] 2014 Jun 28, 6(6):301-312 [viewed 27 September 2014] Available from: doi:10.4329/wjr.v6.i6.301
  4. WEISS KH, PAGON RA, ADAM MP, ARDINGER HH, BIRD TD, DOLAN CR, FONG CT, SMITH RJH, STEPHENS K. Wilson Disease [online] 1993 [viewed 29 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/20301685
  5. MELISH JS, WALKER HK, HALL WD, HURST JW. Thyroid Disease [online] 1990 [viewed 29 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/21250085

Investigations - Fitness for Management

Fact Explanation
Full blood count Even though blood test may not play an important role in diagnosis, it is useful in assessment of nutritional state. As this disease may cause decrease food intake and weight loss that may ultimately leads to nutritional anemia.[1],[2].
References
  1. ROOS RAYMUND A.C.. Huntington's disease: a clinical review. Array [online] 2010 December [viewed 27 September 2014] Available from: doi:10.1186/1750-1172-5-40
  2. WARBY SC, GRAHAM RK, HAYDEN MR, PAGON RA, ADAM MP, ARDINGER HH, BIRD TD, DOLAN CR, FONG CT, SMITH RJH, STEPHENS K. Huntington Disease [online] 1993 [viewed 27 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/20301482

Investigations - Followup

Fact Explanation
MRI brain MRI brain is useful to assess progression of the disease during follow up.[1].
References
  1. WARBY SC, GRAHAM RK, HAYDEN MR, PAGON RA, ADAM MP, ARDINGER HH, BIRD TD, DOLAN CR, FONG CT, SMITH RJH, STEPHENS K. Huntington Disease [online] 1993 [viewed 27 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/20301482

Investigations - Screening/Staging

Fact Explanation
Chorionic villus sampling and amniocentesis Useful in prenatal diagnosis of HD in pregnancy.DNA testing can be carried out obtaining DNA by chorionic villus sampling around 10th and 12th weeks of pregnancy as well as amniocentesis around 15th and 17th weeks of pregnancy.[1].
Stages of HD There are 3 stages of HD. Namely early, middle and late. Symptoms may vary according to the stage. Minor involuntary movements, subtle changes in eye movements, coordination, difficulty in mental planning, and also a depressed or irritable mood recognized in early stage.Chorea can be seen in middle stage with gait disturbances, dystonia, dysphagia and speech difficulties Chorea becomes more prominent in late stage and voluntary activity becomes increasingly difficult.Dysarthria and dysphagia get worsen. And they may also develop bradykinesia .[2].
References
  1. ROOS RAYMUND A.C.. Huntington's disease: a clinical review. Array [online] 2010 December [viewed 27 September 2014] Available from: doi:10.1186/1750-1172-5-40
  2. WARBY SC, GRAHAM RK, HAYDEN MR, PAGON RA, ADAM MP, ARDINGER HH, BIRD TD, DOLAN CR, FONG CT, SMITH RJH, STEPHENS K. Huntington Disease [online] 1993 [viewed 29 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/20301482

Management - General Measures

Fact Explanation
Supportive care Since the patient may developed swallowing difficulty and significant weight loss supportive care is mainly focused on nursing, diet to improve nutrition as well as special equipment.[1].
Physiotherapy Treatment should be carried out in a multidisciplinary approach.Non medical interventions such physiotherapy may give successful outcomes by improving quality of life.[2].
Occupational therapy, and speech therapy Carried out by well speech therapist and a occupational therapist. Play and important role to improve swallowing ability as well as to improve functional outcome.[2].
Avoid certain drugs, Alcohol and smoking L-dopa-containing compounds may increase chorea so best to be avoid and also discourage alcohol and smoking.[1].
Proper counselling, patient and family education Once diagnosis is established patient should be properly counselled.Doctor should explain the nature of the disease, life expectancy and complications. Educate them well regarding the importance of proper follow up. Tell the family members that this is a chronic disease and patient can not do their day today works alone and they may need family members helping hand. Address them about importance of augmentation of nutritional state. Educate them that patient may sometimes need special equipment such as walking aids.[1].
Genetic counseling It is the process of providing individuals and families with information on the nature, inheritance, and implications of genetic disorders to help them make informed medical and personal decisions. Since this is inherited in an autosomal dominant manner the genetic counselling is a must. Family members also have to educate well about the risk of them and their children to get the disease and available diagnostic methods to find them. And educate the patient and family members about the role of family planning.[1].
References
  1. WARBY SC, GRAHAM RK, HAYDEN MR, PAGON RA, ADAM MP, ARDINGER HH, BIRD TD, DOLAN CR, FONG CT, SMITH RJH, STEPHENS K. Huntington Disease [online] 1993 [viewed 27 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/20301482
  2. ROOS RAYMUND A.C.. Huntington's disease: a clinical review. Array [online] 2010 December [viewed 27 September 2014] Available from: doi:10.1186/1750-1172-5-40

Management - Specific Treatments

Fact Explanation
Haloperidol Choreic movements can be partially suppressed by typical neuroleptics including haloperidol .They act by blocking dopamine receptors.[1],[2].
Clozapine and olanzapine They are atypical neuroleptics and have an antichoreatic effect. Act byblocking dopamine receptors. However Clozapine requires white cell control in the blood, so that it is less practical. So olanzapine is widely use. Maximum dose 20 mg.The most common side effects are weight gain and anti-depressive effects. [2].
Tetrabenazine It is a dopamine depleting drug. It also found to reduce chorea. The common side effects are mainly depression and sedation. Maximum dose is 200 mg [2].
Antiparkinsonian drugs Hypokinesia has been tried to treat using antiparkinsonian drugs such as L-dopa. But it almost always gives a very disappointing results. So that dopaminergic drug are not prescribed in practice.[2]. And also those agents found to be increase chorea.[1].
Valproic acid It is found to improve myoclonic hyperkinesia in Huntington disease.[1].
Citalopram and Fluoxetine Use to treat depression and aggression. maximum dose of citalopram is 60 mg in both situations and fluoxetine maximum dose is 60 mg in depression and 200 mg in aggression. [2]. Both of them are selective serotonin re uptake inhibitors.Gastrointestinal disturbances ,dry mouth, headache,excessive sweating and sexual dysfunction are reported side effects.[3].
References
  1. WARBY SC, GRAHAM RK, HAYDEN MR, PAGON RA, ADAM MP, ARDINGER HH, BIRD TD, DOLAN CR, FONG CT, SMITH RJH, STEPHENS K. Huntington Disease [online] 1993 [viewed 27 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/20301482
  2. ROOS RAYMUND A.C.. Huntington's disease: a clinical review. Array [online] 2010 December [viewed 27 September 2014] Available from: doi:10.1186/1750-1172-5-40
  3. FERGUSON JM. SSRI Antidepressant Medications: Adverse Effects and Tolerability Prim Care Companion J Clin Psychiatry [online] 2001 Feb, 3(1):22-27 [viewed 27 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC181155