Major Depression




Difficultlife situations such as losing a close relative or friend, losingjob, or getting through a divorce case are some of the scenarios thatcan make a person become scared, sad, nervous, or lonely. These arenormal receptors to such life stresses. When people experience suchfeelings for no reason, it becomes very difficult for them to carryon with normal life and such people can be viewed to have anxiety ordepression disorder or both. Major depression is an example of suchdisorder. It is a condition whereby an individual feels sad,discouraged, hopeless, or lacks interests in issues that interestedhim or her before. These feelings usually last more than two weeksfor them to warrant medical attention. Major depression isfortunately treatable once it has been diagnosed. In any point intime, it affects 3-5 % of people. It affects about 6.7% of the U.Sadult population in any given year (American Psychiatric Association(2002). It can develop at any age but vast cases begin at 32 yearsand above and affect women more than men. Various medications havebeen developed and are still being improved to cure this disorder.This paper discusses mental disorder, its treatment and presents acomparison of latest clinical research on new drugs in the treatmentof mental disorder.


Itis normal for any other person to feel sad or blue. These feelingsare in most cases short lived and usually end in a couple of hours ordays. When these feelings last more than two weeks, it results in amental disorder referred to as major depression. It is a constantfeeling of hopelessness and despair. With such feeling, it becomeshard to undertake normal life activities such as working, eating,studying, or enjoying the company of friends. To some people, itoccurs once in a lifetime while to others it might occur severally inone’s lifetime. There are other symptoms of major depressionaccording to a manual used in the diagnosis of mental healthconditions. These include loss of energy or fatigue throughout theday, feeling worthless or guilt conscience, insomnia, impaireddecisions, restlessness, suicidal or death thoughts, and significantgain or loss of weight. According to the National Institute of MentalHealth (2009), major depression affects around 6.7 % of the U.S.adults with a close to 20-25 % of adults suffering an incidence ofmajor depression once in their lifetime. It also affects children,teens, and old adults but in most cases it is not diagnosed. Womenare at a higher risk of getting major depression as compared to men.This is attributed to hormonal changes taking place in the life ofwomen as they advance from childhood to puberty and menopause and thedaily life stresses they undergo as they seek to balance familyresponsibilities and career.

Diagnosingand treating major depression.

Thecommon causes of major depression are grief from the loss of a lovedone from death or divorce, isolating oneself from the social groupthey belong, life changes such as retirement or loss of job,conflicts in relationships or family ties, and abuse which could bephysical, sexual or emotional (Akiko, 2008). Once a personexperiences the symptoms associated with major depression, it is veryimportant to have them seek medical attention. A health professional,such as a doctor or psychiatrist performs a thorough medicalexamination and evaluation. The doctor basically enquires about thepersonal and family history which is important in helping identifythe cause of depression. With this information, the doctor may make adecision on whether it is necessary to carry out a depressionscreening test.

Majordepression is fortunately a treatable disorder once tests have beencarried out. Depending on the extent to how the symptoms manifestseverity, the doctor may recommend antidepressant medications fortreatment (Judith, 2004). Psychotherapy or talk therapy may also berecommended depending on the emotional state of the patient. Othermedications are in some cases issued alongside the anti-depressantsto boost its performance. Because certain medications work best forsome people but fail in others, the medical practitioner may beforced to administer different drugs and different doses to identifywhich works well for the patient. In cases where symptoms are severeand the drugs are found to be ineffective, other modes of treatmentare used (Jessica et al, 2011). These are electroconvulsive therapyor shock therapy.


Thevarious types of anti-depressants in the market for treatment ofmajor depression are listed below. It is however important forpatients to discuss and understand the various effects that thesevarious antidepressants pose to the patient with the doctor.Selective serotonin reuptake inhibitors (SSRIs) are an importantantidepressant that the doctors begin by prescribing to patients withmild depression (Steven, 2002). The SSRIs are safer and pose fewerside effects in comparison to other antidepressants. Examples includefluoxetine, paroxetine, sertraline, citalopram, and escitalopram(Jonathan, 2005). The other set of antidepressants are the serotoninand norepinephrine reuptake inhibitors (SNRIs). Examples areduloxetine, venlafaxine, and desvenlafaxine (Jonathan, 2005). Anotherimportant set of antidepressants is norepinephrine and dopaminereuptake inhibitors (NDRIs) with bupropion being a good example. Itis a good antidepressant not associated with sexual side effect likemost antidepressants. Atypical antidepressants form the othercategory of antidepressants which do not fit in any category andincludes trazodone and mirtazapine. They are said to be very sedativeand thus mostly administered in the evenings. Tricyclicantidepressants are among the oldest developed and are rarelyadministered because of the many severe side effects they have onpatients (Georgios et al, 2011). They are given on special occasionswhen the other SSRIS have been tried with no improvement. Monoamineoxidase inhibitors (MAOIs) are on the other hand rarely prescribedbecause of the serious side effects they have on patients. Examplesare tranylcypromine and phenelzine and are administered in caseswhere other antidepressants have failed (Scott &amp Mark, 2009). Itis important to note that other medications may be administeredtogether with antidepressants to improve on their effectiveness.Other antidepressants may as well be prescribed in combination.


Psychotherapygenerally means treating patients by talking out their condition andissues relating to it to a mental health practitioner. It is alsoreferred to as talk therapy, psychosocial therapy or counselling.Different types of psychotherapy are interpersonal therapy, dialecticbehavioral therapy, cognitive behavioral therapy, commitment andacceptance therapy, and mindful techniques (John, 2007). Thesepsychotherapies are important because they help a patient adjust to acurrent difficult situation, point out negative behaviors and beliefsand in return replace them with healthy ones, discover better ways ofcoping and dealing with challenges in life, explore relationships andbetter ways of interacting with those around them, regain lost senseof self satisfaction and devise ways of easing symptoms associatedwith depression, be in a position to accept and deal with life’sdistress in healthy ways, and point issues causing depression and howto handle them.

Electroconvulsivetherapy (ECT)

Inthis type of treatment for major depression, electric currents arepassed through the brain of the patient. The process is believed toinfluence the levels of neurotransmitters in the brain and offerrelieve on severe depression and which other medications have failedto work (Daniel, 2010). Although it is accompanied by side effectssuch as headaches, one can tolerate them. To other patients, itcauses memory loss which is short lived. It is a good form oftreatment for patients who have tried other medications in vain. Itis also useful to patients whom for health reasons are not in aposition to take antidepressants or their symptoms are at theriskiest point in life and worse still at the point of committingsuicide.

Transcranialmagnetic stimulation (TMS).

Thisis mostly a treatment option for major depression patients whosecondition does not seem to respond to the medication administered. Inthis form of treatment, a patient is sat on a reclining chair with atreatment coil aligned against the scalp (Akiko et al, 2008). Thecoil then sends brief magnetic pulses that in turn stimulate nervecells in the brain that are responsible for mood regulation anddepression.


Neurocognitiveeffects of ketamine in treatment – resistant major depression:association with antidepressant response.

Jameset al (2013) carried out a study to examine the impact of ketamine inthe treatment of major depression. According to the research study,ketamine was observed to show a rapid antidepressant effect withinhours or days after administering the drug treatment resistantdepression. A neurocognitive assessment was carried out on 25patients with treatment resistant depression. It was carried out inconjunction with a clinical trial with single open clinicaladministration of ketamine in patients with TRD. The 25 participantswent through a psychiatric and medical screening after undergoingcomplete informed consent process.

Thestudy participants were diagnosed to have major depressive disorderwhich was chronic and recurring after treatment. They underwent abattery of neurocognitive test a week before single IV infusion ofketamine hydrochloride, 0.5mg/ kg in a period of 40 minutes wasadministered (James et al, 2013). After the lapse of the 40 minutes,a series of neurocognitive tests were carried out. The potentialclinical utility shows an association between neurocognition andketamine response thus showing a presence of specific neurobiologicalcharacteristics among the treatment responders. Acute impact ofketamine on neurocognition in treatment resistant disorder wasobserved.

Theparticipants had moderate case of major depression. The participantshad failed to respond to prior treatment of the antidepressantsadministered to them. Those who had taken psychotropic medicationwere subjected to a washout before infusion of the ketamineantidepressant. After the forty minute infusion of the ketamineantidepressant, the changes in the severity of the depressivesymptoms were measured. The response rate was greater than 50% in thefirst twenty four hours (James et al, 2014). The side effects werealso measured using the brief psychiatric rating scale. Before theinfusion of ketamine, patients were administered with a single doseof either lamotrigine 300 mg through the mouth to test on the effectof lamotrigine on the neuropsychiatric effects of ketamine.

Effectsof ketamine on major depressive disorder in a patient withposttraumatic stress disorder

Arthur,2013 carried out a study to determine the effect of ketamine on apatient with major depressive disorder. His study shows that ketaminehas recently seen a revitalization of use. In the study, a singlepatient with a history of severe depression and combat relatedpost-traumatic stress disorder. The patient’s case was unresponsiveto oral medication administered before. The patient had developedPost traumatic syndrome disorder experiencing insomnia, loss offamily interest, and two cases of suicide.

Apatient was brought to a clinic and diagnosed with post traumaticsyndrome disorder and chronic and major depressive disorder. An IVline was started, and the patient was given midazolam, 3 mg (0.04 mg/kg) with the IV as the pre-induction medication (Arthur, 2013). Themidazolam showed an anxiolytic effect as evidenced by the relaxedposturing and verbal admission of relaxation. 70 mg (1mg/ kg) ofpropofol was administered with a combination of an IV bolus of 30 mgof lidocaine (Arthur, 2013). A hypnotic state was achieved as shownby loss of eyelid reflex. A 20 minute infusion by IV piggyback wasadministered of propofol, 30mg with an infusion rate of 20 µg/ kg/min, and ketamine 35mg. After the administration, the patient wasobserved to maintain spontaneous respirations with no need for oraland nasal adjuncts (Arthur, 2013).

Thepatient was arousable and responded appropriately to the verbalstimuli fifteen minutes after the completion of the infusion. Afteran hour with observation of vital signs after every fifteen minutes,the patient was observed to be responsive to verbal stimuli. Althoughthe patient claimed to have trouble focusing his vision, he was awakeand conversant by this time. There was a notable improvement in hismental condition and he could be seen smiling and making jokes withthe medical attendants at the hospital. He also became affectionatewith his wife and could be seen touching her belly as she waspregnant. All these characters demonstrated an improvement in hismental condition. In an hour’s responsiveness time, the IV line wasremoved. His walk was steady and he was able talk withoutdifficulties. After 30 minutes under observation, the patient wasdischarged from the hospital. He only complained of slight headacheafter complete infusion (Arthur, 2013). With follow up by apsychiatrist, the patient was observed to have his sleep normalize.The nightmares he experienced were now gone with no cases ofinsomnia. He also experienced joy in his life unlike before andexperienced greater satisfaction of life.

Multistagedrug effects of ketamine in the treatment of major depression

Agood number of patients diagnosed with major depression disorder donot show response to the standard anti depressive treatmentsadministered to them. Recent studies have showed that ketaminepromotes a rapid and sustained anti depressive effect in thetreatment of resistant depression. According to the study by Martinet al (2014) ketamine which is an antagonist of N – methyl D-aspartate receptor is a rapid anti-depressant targeting the glutamatesystems. Clinical trials on patients with major depression have shownthat a single trial of low- dose ketamine has a rapid anti-depressantresponse one day after an infusion lasting 7 days.

Therapid effect of ketamine is observable in patients with treatmentresistant depression (Martin et al, 2014). A good number of studiesshow fast and high efficiency of use of ketamine in the treatment oftreatment resistant depression. The duration of the side effectsreported to be prevalent for a week is now reduced to two to threedays in the recent meta-analyses.

Themechanism and predictors of ketamine’s antidepressant action

Theearly responses of the use of ketamine in the treatment of ketaminewere associated positive long term outcome. Previous studies showthat ketamine was previously observed to show an increase in localglutamine concentration in anterior cingulate cortex. This is thesame area where more treatment resistant depression patients wereshown to exert a local glutamine deficit. The convergence of earlyanti-depressants of other glutamatergic modulates which as well showchanges in the cingulate glutamine concentrations. Studies showevident early response after ketamine was predicted by lower measuresof local glutamine concentration before treatment. Sub anestheticketamine infusion was observed to show fast antidepressant effects.The effects are mediated by glutamatergic mechanisms which involveregional processes in the cingulate cortex classifying responsetendencies and sub types in major depressive disorders.

TheAMPA/ kinase receptor can be stimulated by the blockage of NMDAreceptors and increased extracellular glutamate levels with low dosesof ketamine. Researches have shown that AMPA receptors play a verycritical role in the ketamine – related anti-depressant effects. Ablockage of the antidepressant effect of ketamine can be induced bythe subcutaneous treatment with the AMPA receptor antagonist 2,3-dihydroxy-6-nitro-7-sulfomoylbenxo (f) quinoxaline (M). Again, inthe chronic treatment of major depression, low doses of ketamineresult in an increase in the AMPA/ NMDA receptor density ratio inhippocampus. When administered in low doses, ketamine still activatesthe mammalian target of the rapamycin pathway in post synapse.

Comparisonand contrast in the three research papers

Becauseof the repeated cases of major depression despite the application anduse of antidepressants in its treatment, there has been a need toimprove on them or better still introduce and promote the use of anew mode of treatment. This improvement of a new drug for thetreatment of major depression should be efficient, safe and with fewadverse side effects. The use ketamine in combination with otheranti- depressants has been observed to be efficient and safe form oftreatment with rare side effects with most of them disappearing asthe treatment continued. In their article on Neurocognitive effectsof ketamine in treatment – resistant major depression: associationwith antidepressant response, the authors presented a study on theefficiency and safety in use of ketamine. The study clearlydemonstrated effectiveness of use of ketamine as a drug for treatmentwith minor side effects as compared to the use of otherantidepressants which had adverse effects on the patients with somereporting reoccurrence of the disorder even after completing therecommended dose.

Onthe study on effects of ketamine on major depressive disorder in apatient with posttraumatic stress disorder by Arthur, (2014). Heshowed how the use of ketamine in the treatment of recurrent majordepressive disorder was cured after infusion of the drug incombination with midazolam and an IV line pre- induction. The patientunder study was observed to recover from the effects of majordepressive syndrome and enjoying life’s activities unlike the casesbefore where he had not observed a change in the previous treatmentusing different anti-depressants.

Theresearch on Multistage drug effects of ketamine in the treatment ofmajor depression by Martin et al, 2014 shows how ketamine can be aneffective method of treatment for major depression once combined withother treatments. It clearly brings out that the use of mostantidepressants over the years have not been in a position to clearlytreat major depression with a good number of cases being recurrentdespite their use. The study presents various cases under which theuse of ketamine in combination with other drugs can help ease theeffects of the symptoms of major depression and thus curing thedisorder. The study concluded that despite the previous studies thatketamine could not be helpful in curing the major depressivedisorder its combination with other drugs would be very effective incuring the disorder although with some side effects to the patients.

Allthe three studies led to the conclusion that medical practitionershave a new improved drug for the use in the treatment of majordepression. The three studies clear show that the use of ketamine iseffective as long as the case of each particular patient isidentified correctly and thus the correct combination and dosage ofketamine administered. The side effects are not long lived and thepatients under study were observed to cope with them. The proceduresapplied where almost similar depending on the extent of thedepressive symptoms. This in turn helped ease the symptoms of majordepression thus helping the patients recover from the disorder. Inall study cases, an approval from the relevant authorities wassought. The patients who were used as the sample for study were alsoenlightened on the procedure and presented with consent forms whichthere were supposed to sign before the start of the study.

Theresearch was also met by some limitations. The cases of the patientsused as sample dropping out of the study were a limiting factor. Thisto some extent would ruin the process and thus loss of believe in theuse of ketamine in the treatment of major depression. This is becausethe drop out cases was as a result of lack of response of thetreatment to the patients. Other patients also dropped out of thestudy because of the adversity of the side effects on their health.Some experienced insomnia, numbness, dizziness and nausea. It washowever fortunate that some of the patients were willing to continuewith the study despite the effects. There is also a need to have thestudy involve a large number of the patients for more accurateresults.

Impactof the study on use of ketamine as an improved drug for treatment ofmajor depression

Thesestudies on the use of ketamine in combination with other drugs in thetreatment of major depression have a positive impact for use of thistreatment in clinical practice. Over the years, the medicalpractitioners have had big challenge in dealing with major depressioncases which did not seem to respond to the use of the otherantidepressants. Most patients reported recurrence of the disorderdespite undertaking the complete dose while others had experiencedadverse side effects after using different antidepressants as atreatment form for major depression. This was an overwhelming factfor the medical practitioners whose desire is to have their patientsrecover fully from the disorder being treated. After the study, themedical practitioners now have a new solution to this problem. Thestudies proved on the efficiency and safety of use of ketamine as aform of treatment with few adverse side effects most of which aretolerable.

Fundingof the research projects

Thefact that the recurrence cases for major depression even aftercompleting a treatment was a concern for all stakeholders in thehealth sector. This means that there was a dire need for developmentof a new or improvement of the existing form of treatments for thisdisorder. This means that the stakeholders in this sector would findit promising to fund projects whose intention was to help in findinga solution for the menace brought about by this disorder. Suchstakeholders include ministry of health, FDA, the local ethicscommittee of a particular region.


Mostof the disability and impairment cases have been because of the majordepression disorder. For quite a while, treatment of major depressionhas been a source of headache for various medical practitioners inthe U.S. The use of most antidepressants in its treatment has provenfruitless in most cases with a lot of recurrence of the disorder.Other patients have developed serious and adverse effects to the drugforcing them to discontinue use yet still experiencing the effects ofthe symptoms of the disorder. As a result, various scholars andmedical practitioners have developing a desire in carrying outstudies in their quest to find a solution to this disorder. Somescholars have proposed the improvement of these antidepressants ofthe use of other methods in the treatment of major disorder such aspsychotherapy, Transcranial Magnetic Stimulation, electroconvulsivetherapy, or shock therapy.

Theuse of ketamine in combination with other drugs has been the core ofthis study as well as the clinical researches presented here. Thevarious articles have demonstrated the effectiveness of the use ofketamine recently with combination with other drugs as opposed to theuse of the other antidepressants singly. The use of most of theantidepressants resulted in adverse side effects and recurrence ofthe disorder in most cases. This was proved to be the contrary withuse of ketamine after its combination with different drugs in thetreatment of the disorder. The method did not present adverse sideeffects to the patients. Most of the side effects were mild and coulddisappear as the treatment continued and the patients could as wellstand them. The studies carried out need however need to be repeatedwith a larger sample group for more accurate results. The fact thatsome patients did not respond to the treatment could be a basis forcriticism and thus need for a larger sample. There is also a need tocarry out more research on the treatment of major depression becauseof the few cases that dropped out of the study due to lack ofresponse in the treatment and also the adverse effects of thetreatment.

Theuse of the drug is limited because it has some adverse effects tosome patients who have been administered the drug even in combinationwith these other drugs, The questions remaining unanswered is whatbecomes of the people who still do not seem to benefit from the useof ketamine? And what happens to the patients experiencing adverseeffects from the use of ketamine?


Akiko,F. Et al. (2008). Adequacy of continuation and maintenance treatmentsfor major depression in Japan. Journalof psychopharmacology.Vol. 22, No. 2. Pp 153-156

Arthur,L. (2013). Effects of ketamine on major depressive disorder in apatient with posttraumatic stress disorder. AANAjournal.Vol. 13, no. 1. Pp 113-127

AmericanPsychiatric Association (2002). Generalized anxiety disorder.Diagnosticand Statistical manual of mental disorders: DSM-IV-TR

Brandon,A. et al. (2012). An open trial of a new acceptance – basedbehavioral treatment for major depression with psychotic features.Psychosocialresearch program. Vol.37, No. 3. Pp 324-355

Daniel,N. (2010). Chronic Depression: Diagnosis and Classification. CurrentDirections in Psychological Science. Vol.19, No. 2. Pp 96-100.

Georgios,P. Et al. (2011). Treatment with paroxetine, but not amitriptyline,lowers levels of lipoprotein (a) in patients with major depression.Journalof psychopharmacology. Vol.25, No. 10. Pp 1344-1346

James,W. et al. (2014). Neurocognitive effects of ketamine in thetreatment- resistant major depression: association withantidepressant response. Journalof psychopharmacology. Vol.23, no. 1. Pp 481-488

Jessica,A. Et al. (2011). Evaluating the Clinical Significance of DepressionTreatment: Implications for Global Mental Health Research.InternationalJournal of Mental Health. Vol.40, No. 3. Pp 3-28

John,P. et al. (2007). Depression: New perspectives on treatment andetiology. Biologicalpsychiatry. Vol.62, No. 11. Pp 1208-1216

Jonathan,R. (2005). Mood and Emotion in . CurrentDirections in Psychological Science. Vol.14, No. 3. Pp 167-170

Judith,N. (2004). Gender Bias in the Diagnosis and Treatment of Depression.InternationalJournal of Mental Health. Vol.33, No. 2. Pp 32-43.

Martin,W. et al (2014). Multistage drug effects of ketamine in the treatmentof major depression. Springerjournals. Vol.26, no. 1. Pp 55-65

NationalInstitute of Mental health. (2009).http//

Scott,M. &amp Mark, W. (2009). Life Stress and . CurrentDirections in Psychological Science. Vol.18, No. 2. Pp 68-72

Steven,D. et al. (2002). Treatment and Prevention of Depression.PsychologicalScience in the Public Interest. Vol.3, No. 2. Pp 39-77

Yvonne,T. Et al. (2006). Daily and Spaced Treatment with TranscranialMagnetic Stimulation in : A Pilot Study. Australianand New Zealand Journal of Psychiatry. Vol.40, No. 9. Pp 759-763