Motivation and emotion/Book/2021/Amotivational syndrome

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Amotivational syndrome:
What is amotivational syndrome and how can it be treated?
Figure 1. Most individual's exhibiting signs of amotivational syndrome will find it harder than normal to get things done. Increasingly finding it very difficult to get moving or reduced emotional reactivity to pressure situations are signs of feeling unmotivated than normal.

Overview[edit | edit source]

Amotivational Syndrome (also referred to as apathy syndrome) is an affective disorder variant which is caused by continuous use of cannabis or other selective serotonin reuptake inhibitors (SSRIs) which then result to certain cognitive impairments and dopaminergic underactivity [1] similar to those exhibited in patients with schizophrenia and depression[2]. Characteristics associated with it are gradual detachment from reality or the outer world, and loss of emotional reactivity, drives and aims. Other behavioural changes observed are the blunted responsiveness to outer stimuli and the inability to experience enjoyment without using cannabis[3]. Research also shows links between impeded memory and attention, and amotivational syndrome [4]. Depending on the substance used, amotivational syndrome stems from two main sources. The first linking prolonged usage or developed dependency towards cannabis or marijuana usage [4] and the second subtype linking SSRIs and its potential side effect of inducing apathetic behaviours on patients it is prescribed to [5].

Signs and symptoms[edit | edit source]

Multiple research results agree that degeneration of the frontotemporal lobar region can be attributed to increased apathy[6][7]. Changes in frontal lobe activity also suggest that substances associated with the syndrome affect the prefrontal cortex.[8] Other signs of being affected by amotivational syndrome report greater blood oxygen level dependency, and changes in neural functioning due to increased dopamine releases to the shell area of the nucleus accumbens. Apart from that, activation of the cannabinoid receptor type 1 (CB1) is done which then affects areas such as the basal ganglia, cerebellum, and hippocampus which then alters the amplification of activities of gabaergic, glutamatergic, and dopaminergic systems as a result to exposure from substances like cannabis[9].

Researchers note that when studying patients with amotivational syndrome, they exhibit very similar negative symptoms to that of patients with schizophrenia[10] and depression.[11] These number of negative symptoms include: blunted emotional responses or sometimes complete levels of emotional withdrawal, poor rapport, passive/apathetic social withdrawal, difficulty in abstract thinking, lack of spontaneity/flow of conversation, affective flattening[12]. Overall, loss of motivation is one of the top symptoms for the syndrome but it is important to note that this motivational loss should not be attributed to any other factors such as emotional distress, intellectual impairment, or a diminished level of consciousness as having motivational loss to these factors will classify them as symptoms for apathy altogether[13].

Amotivational syndrome type[edit | edit source]

Figure 2: Cannabis use may alter the function of the dopamine release systems.

Cannabis use or dependent amotivational syndrome[edit | edit source]

Due to cannabis altering the function of the dopamine release systems, there is a reduced amount of release for it in the reward system area. This link between desensitisation and down-regulation is associated with the activation of CB1 receptors which are ingrained with people's DNA.[14] Other sources also find that these changes are connected with the development of anhedonia and the lack of sensitivity felt before from pleasant stimuli which suggest that exposure to cannabis revises reward system sensitivity[15].

Multiple debates on the topic of associations between cannabis use and motivation loss for a while with studies from as far back as 1976 [16] to present times. There is however research criticising the existence of amotivational syndrome reactions to cannabis. There are arguments combating cannabis use as not causing apathetic behaviours, but in fact facilitating a cognitive style change, coupled with cannabis' ability to alter attention states, and a specific personality factor with increased susceptibility referred to as "trait absorption". With that, they argue that this initial change may have been coupled with pre existing depressive feelings that may be mistaken as amotivational syndrome rather than considering personality.[17] Moreover, when looking at marijuana users with depression, a study finds that development of amotivational syndrome in marijuana users were observed due to diagnosed depression amongst their participants[18]. This implies that the combination of depression and marijuana use developed amotivational symptoms and not merely just the usage of marijuana.

Figure 3. SSRI fluvoxamine depromel in it's packed and tablet form.

SSRIs-induced amotivational syndrome[edit | edit source]

It has proven difficult to identify mechanisms involved in instilling apathetic behaviours in patients as not all of the patients taking the medication get amotivational syndrome symptoms. Thus, it implies that more than the drug, neurophysiological or pharmacokinetic vulnerabilities are involved in the apathetic behaviour

There are two possible suggestions of which parts were affected by the disorder. In a study following the after-effects of clients that were prescribed fluvoxamine and fluoxetine, they found that frontal lobe activity via serotonergic systems were being modified by SSRIs and that these affected serotonergic systems led to modifying midbrain dopaminergic systems which project onto the prefrontal cortex [19]. The above line of activity then triggered the symptoms synonymous to individuals suffering from apathy syndrome.

Apathy among the participants of another cross-sectional study were also assessed using the Apathy Evaluation Scale (AES). Using the AES, a range of 18-72 scores were recorded among the participants with scores greater than 30 being considered as clinically significant apathy. The findings of the study indicated that patients who were treated with SSRIs had a higher mean apathy score than those who were not treated with SSRIs, creating a significant link between the use of SSRIs and clinically significant apathy[20].

It is important to note that amotivational syndrome symptoms share similarities with symptoms of depression such as loss of motivation. Given these similarities, different indices are utilized in order to distinguish one diagnosis from the other. A clinical version of Apathy Evaluation Scale or AES-C is used to detect apathy while indices such as Hamilton Rating Scale for Depression and the Beck Depression Inventory are used for detect feelings and symptoms indicative of depression[21]. The use of the AES-C involves various subdomains such as motivation, novelty-seeking, and persistence wherein scores are derived based on patients’ answers to questions and queries[22].

Treatment options[edit | edit source]

Cannabis subtype options[edit | edit source]

As cannabis dependence is one of the major factors for prolonged usage and eventually leads to development of amotivational symptoms, treatment for drug addiction is recommended. By addressing the volume of consumption, it will give less opportunities for the drug to alter motivation and help clients seek healthier recreational or coping options. Older options for treatment showed that caerulein injections were effective in a case study of a heavy marijuana user and showed that after two once-a-week doses of caerulein, they found signs of improvement of symptoms[23]. Another research on methadone's effectivness on detoxifying drug addicts produced results in their trial indicating the drug's potential in reduction of withdrawal symptoms, reduction amotivational symptoms, and initiation of treatment processes to the addiction[24]. So overall, the most useful treatment for amotivational syndrome caused by cannabis use is reduction of usage and dependence.

SSRIs subtype options[edit | edit source]

Mitigating the severity of SSRI-induced amotivational syndrome symptoms generally involves a tapering of dosages until eventual discontinuation. Recommendations for handling people affected by SSRI-induced amotivational syndrome usually start with monitoring the dosages given. Patients are scheduled for follow-up meetings with their psychiatrists until an effective dose ratio is achieved. These visits also couple as important opportunities for psychiatrists to examine clients for the presence of amotivational syndrome symptoms and to consider other potential causes of the apathy.[25]

Three possible strategies are presented by Barnhart and colleagues (2004) to be tailored to each patient[26]:

  1. Titration of SSRI dosage
  2. Augmentation
  3. Switching of different class of antidepressant

Multiple studies have tested the right amounts of SSRI dosages to safely give patients which also passed for dispensation due to the results that the dosage was enough to control symptoms and was below thresholds causing apathy syndrome. For short term medication changes, titration of current SSRIs prescribed may be warranted especially if levels of effectivity are not reached. If that is unsuccessful, augmentation using bupropion has been helpful in some cases[27]. If that does not work either, there are studies that provide alternatives for clients that monoamine oxidase inhibitors or tricyclic antidepressants [28], and clomipramine [29] do not induce apathetic symptoms even if clomipramine is considered a strong SSRI. Sulpiride [30] and olanzapine [31] have also been used to improve SSRI-induced motivational issues but reports of it's effectivity have been limited. Studies also show that discontinuation of SSRI treatments, particularly citalopram and fluoxetine, decreases debilitating symptoms of amotivation and apathy. In a study by Padala and colleagues (2012), six different participants who showcased high scores in the AES-C were subjected to tapering and eventual discontinuation of their SSRI treatments. Recovery from symptoms of SSRI-induced apathy syndrome ranged from 2 weeks to 2 months[32].

Current research and study challenges[edit | edit source]

Cannabis subtype options[edit | edit source]

Though studies assert cannabis' role in reducing motivations from its users, other researchers from the 2000s question the validity of the conclusions which these early studies into cannabis have found and whether or not the negative impacts of the drug were as severe as reported. Barnwell and colleagues (2006)[33] found that in their sample of 487 people that were strictly divided into two groups of users and non-users of marijuana, the results showed no differences in motivation level. They instead found a difference in subjective well being where a slight decrease of it was observed and does reflect that motivation issues should be associated with well being of users rather than on the consumption of the drug. [34]. More recent studies in the past decade, however, reassert the negative consequences of dependent and even acute users of cannabis rather than the positive effects some earlier studies have claimed.

With the general acceptance of cannabis as a ‘soft drug’ a rising number of college students have taken to using the drug recreationally. One consequence, however, is the rising rate of amotivational syndrome reported among students who use marijuana recreationally[35]. Coupled with alcohol and tobacco use, the drug has been linked to lower educational performance and heightening the risk of depression and suicidal ideation[36]. Chronic and dependent cannabis use has also been reported in slowing down cognitive functions, negatively impacting memory retention, and high levels of apathetic behavior as well as a number of other psychological and physical side effects apart from amotivational syndrome[37]. As such, due to its recent decriminalization in certain parts of the globe, cannabis research has yet to reach nuanced and in-depth scientific analysis. In this regard, the psychopathological effects - both short term and long term - have yet to be fully mapped out by research[38].

SSRIs subtype options[edit | edit source]

Recent studies have made progress in understanding the overarching effects of SSRI treatments across different age groups and people of varying conditions. A 2019 study by  Hye-Geum Kim  and colleagues[39] also reiterated the findings of Padala and colleagues that a reversal of A 2021 study by Mortensen and Andersen[40] focused on the risk and precautions that comes with the prescription of SSRI treatments for people with cardiovascular conditions such as stroke and myocardial infarction. Long-term effects of SSRI even after discontinuation are also being considered as conditions termed as withdrawal syndrome or discontinuation syndromes have been suggested. Through mainly case reports, symptoms indicative of withdrawal syndrome include sensory and gastrointestinal symptoms, somatic symptoms, and psychological symptoms[41]. Somatic symptoms include lethargy and dizziness while psychological symptoms include anxiety and poor concentration. These symptoms were reported within a week after discontinuation with some being reported months after discontinuation. However, there is no evidence to date that indicates a link between the severity of symptoms and the length of SSRI treatment. Further studies are needed to expand on this topic.

Test your knowledge[edit | edit source]

The reason why it's difficult to study factors that associate with amotivational syndrome is because:

Not all people taking the substances develop the syndrome, thus implying that other factors could be the cause of amotivational syndrome.
The technology to determine the specific parts of the brain affected when taking marijuana has not been developed yet and it's process is slow due to the issues surrounding studying law problematic drugs such as marijuana.
The brain is too complicated to understand and even if people got results, they don't know how to interpret them.


Conclusion[edit | edit source]

To summarize, amotivational syndrome is a mental disorder stemming from substance use wherein individuals who regularly partake in cannabis or who have regular prescriptions of SSRIs are possibly affected by it. Signs include: changes in the frontotemporal lobar region and parts associated with altering neural functions which then affect the dopaminergic activity in the brain. Symptoms are loss of motivation or emotional reactivity, blunted reactions to outer stimuli, poor rapport or social skills, increased difficulty for abstract thinking and attention, and decreased memory skills.

Other things discussed are the prevalence of multiple observations overtime of the connection between cannabis to apathetic behaviours to which formed the studying of amotivational syndrome as a result to regular use. Discussions on the effects of marijuana's effects being absorbed differently from others due to some individuals having higher trait absroption is considered. Other challenges touched are that cannabis usage cannot be the only factor to consider when looking at the causation of amotivational syndrome and encourages thoughts on looking for other neurophysiological or pharmacokinetic vulnerabilities. Discussions for the side effects of SSRI medications on patients are also challenged wherein they experienced amotivational symptoms once the regular prescription took place and saw effects of the amotivational side effect wear off once a patient was given time to recuperate and taken off of the prescription for them.

Treatment options for both of the substances showed that by reducing the amounts taken, it is expected that symptoms for the amotivational syndrome would gradually get reduced as well. It is also discussed that looking into totally discontinuing use is also effective and taking part in drug addiction therapy would help in doing so. Mentions for three specific other options to consider for treatment of SSRI-induced amotivational syndrome are by titration of the medication, augmenting it, or by switching the medication all together. It is also recommended that people prescribed an SSRI have multiple follow up consultations schedule to give psychiatrists a chance to monitor the side effects experienced by the patient.

As for current research, trends of the rise of marijuana as a common soft drug for college students are recognized and research takes a stand of finding warning signs that even recreational users are not excluded from feeling amotivational symptoms such as slowed cognitive functioning. Current research also look at combinations of cannabis with other substances such as alcohol and tobacco and find the effects concerning due to the combo increasing suicide ideation and depression. Due to the current move to decriminalise marijuana, researchers are looking at expanding their observations on larger populations of users which may produce more accurate results for studies on the drug's effects on the public.

Recent research on SSRIs produced findings on multiple age groups and conditions and are finding more probable side effects such as cardiovascular health issues. Also, though there is mention of one of the treatment options being discontinuing the use of SSRIs to reduce amotivational symptoms, doing so may increase likelihood for patients to suffer from withdrawal syndrome or discontinuation syndrome. With that it also finds that discontinuation symptoms can show up immediately or even up to months after discontinuation and recommendations to study this issue further have been mentioned.

See also[edit | edit source]

References[edit | edit source]

  1. Lewine, R. (1985). Schizophrenia: An Amotivational Syndrome in Men. The Canadian Journal of Psychiatry, 30(5), 316–318. https://doi.org/10.1177/070674378503000503 ‌
  2. Rovai, L., Maremmani, A. G. I., Pacini, M., Pani, P. P., Rugani, F., Lamanna, F., Schiavi, E., Mautone, S., Dell’Osso, L., & Maremmani, I. (2013). Negative dimension in psychiatry. Amotivational syndrome as a paradigm of negative symptoms in substance abuse. Rivista Di Psichiatria, 48(1), 1–9. https://www.rivistadipsichiatria.it/archivio/122 8/articoli/13610/ ‌
  3. Rovai, L., Maremmani, A. G. I., Pacini, M., Pani, P. P., Rugani, F., Lamanna, F., Schiavi, E., Mautone, S., Dell’Osso, L., & Maremmani, I. (2013). Negative dimension in psychiatry. Amotivational syndrome as a paradigm of negative symptoms in substance abuse. Rivista Di Psichiatria, 48(1), 1–9. https://www.rivistadipsichiatria.it/archivio/122 8/articoli/13610/ ‌
  4. 4.0 4.1 Blum, K., Braverman, E. R., Holder, J. M., Lubar, J. F., Monastra, V. J., Miller, D., Lubar, J. O., Chen, T. J. H., & Comings, D. E. (2000). The Reward Deficiency Syndrome: A Biogenetic Model for the Diagnosis and Treatment of Impulsive, Addictive and Compulsive Behaviors. Journal of Psychoactive Drugs, 32(sup1), 1–112. https://doi.org/10.1080/02791072.2000.10736099
  5. Padala, P. R., Padala, K. P., Majagi, A. S., Garner, K. K., Dennis, R. A., & Sullivan, D. H. (2020). Selective serotonin reuptake inhibitors-associated apathy syndrome. Medicine, 99(33), e21497. https://doi.org/10.1097/md.0000000000021497 ‌
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  10. Lewine, R. (1985). Schizophrenia: An Amotivational Syndrome in Men. The Canadian Journal of Psychiatry, 30(5), 316–318. https://doi.org/10.1177/070674378503000503 ‌
  11. Rovai, L., Maremmani, A. G. I., Pacini, M., Pani, P. P., Rugani, F., Lamanna, F., Schiavi, E., Mautone, S., Dell’Osso, L., & Maremmani, I. (2013). Negative dimension in psychiatry. Amotivational syndrome as a paradigm of negative symptoms in substance abuse. Rivista Di Psichiatria, 48(1), 1–9. https://www.rivistadipsichiatria.it/archivio/122 8/articoli/13610/ ‌
  12. Bersani, G., Bersani, F. S., Caroti, E., Russo, P., Albano, G., Valeriani, G., Imperatori, C., Minichino, A., Manuali, G., & Corazza, O. (2016). Negative symptoms as key features of depression among cannabis users: a preliminary report. European Review for Medical and Pharmacological Sciences, 20(3), 547–552. https://pubmed.ncbi.nlm.nih.gov/26914132/ ‌
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  19. Hoehn-Saric, R., Lipsey, J. R., & McLeod, D. R. (1990). Apathy and indifference in patients on fluvoxamine and fluoxetine. Journal of Clinical Psychopharmacology, 10(5), 343–345. https://pubmed.ncbi.nlm.nih.gov/2124218/ ‌
  20. Padala, P.R., Padala, K.P., Majagi, A.s., Garner, K.K., Dennis, R.A., & Sullivan, D.H. (2020). Selective serotonin reuptake inhibitors-associated apathy syndrome. Medicine, 99(33), e21497. https://doi.org/10.1097?md.0000000000021497
  21. Kim, H. G., Koo, B. H., Lee, S. W., & Cheon, E. J. (2019). Apathy syndrome in a patient previously treated with selective serotonin reuptake inhibitors for depression. Yeungnam University Journal of Medicine, 36(3), 249–253. https://doi.org/10.12701/yujm.2019.00150
  22. Padala, P. R., Padala, K. P., Monga, V., Ramirez, D. A., & Sullivan, D. H. (2012). Reversal of SSRI-Associated Apathy Syndrome by Discontinuation of Therapy. Annals of Pharmacotherapy, 46(3), 452. https://doi.org/10.1345/aph.1q656.
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  25. Barnhart, W. J., Makela, E. H., & Latocha, M. J. (2004). SSRI-Induced Apathy Syndrome: A Clinical Review. Journal of Psychiatric Practice®, 10(3), 196–199. https://journals.lww.com/practicalpsychiatry/Fulltext/2004/05000/SSRI_Induced_Apathy_Syndrome__A_Clinical_Review.10.aspx ‌
  26. Barnhart, W. J., Makela, E. H., & Latocha, M. J. (2004). SSRI-Induced Apathy Syndrome: A Clinical Review. Journal of Psychiatric Practice®, 10(3), 196–199. https://journals.lww.com/practicalpsychiatry/Fulltext/2004/05000/SSRI_Induced_Apathy_Syndrome__A_Clinical_Review.10.aspx ‌
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  31. Marangell, L. B., Johnson, C. R., Kertz, B., Zboyan, H. A., & Martinez, J. M. (2002). Olanzapine in the treatment of apathy in previously depressed participants maintained with selective serotonin reuptake inhibitors: an open-label, flexible-dose study. The Journal of Clinical Psychiatry, 63(5), 391–395. https://doi.org/10.4088/jcp.v63n0503 ‌
  32. Padala, P. R., Padala, K. P., Monga, V., Ramirez, D. A., & Sullivan, D. H. (2012). Reversal of SSRI-Associated Apathy Syndrome by Discontinuation of Therapy. Annals of Pharmacotherapy, 46(3), 452. https://doi.org/10.1345/aph.1q656.
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  34. Barnwell, S., Earleywine, M., & Wilcox, R. (2006). Cannabis, motivation, and life satisfaction in an internet sample. Substance Abuse Treatment, Prevention, and Policy, 1(1), 2. https://doi.org/10.1186/1747-597x-1-2
  35. Lac, A., & Luk, J. W. (2017). Testing the Amotivational Syndrome: Marijuana Use Longitudinally Predicts Lower Self-Efficacy Even After Controlling for Demographics, Personality, and Alcohol and Cigarette Use. Prevention Science, 19(2), 117–126. https://doi.org/10.1007/s11121-017-0811-3
  36. Pacheco-Colón, I., Ramirez, A. R., & Gonzalez, R. (2019). Effects of Adolescent Cannabis Use on Motivation and Depression: a Systematic Review. Current Addiction Reports, 6(4). https://doi.org/10.1007/s40429-019-00274-y
  37. Schmits, E., & Quertemont, E. (2013). [So called “soft” drugs: cannabis and the amotivational syndrome]. Revue Medicale de Liege, 68(5-6), 281–286. https://pubmed.ncbi.nlm.nih.gov/23888577/
  38. Volkow, N. D., Swanson, J. M., Evins, A. E., DeLisi, L. E., Meier, M. H., Gonzalez, R., Bloomfield, M. A. P., Curran, H. V., & Baler, R. (2016). Effects of Cannabis Use on Human Behavior, Including Cognition, Motivation, and Psychosis: A Review. JAMA Psychiatry, 73(3), 292. https://doi.org/10.1001/jamapsychiatry.2015.3278
  39. Kim, H. G., Koo, B. H., Lee, S. W., & Cheon, E. J. (2019). Apathy syndrome in a patient previously treated with selective serotonin reuptake inhibitors for depression. Yeungnam University Journal of Medicine, 36(3), 249–253. https://doi.org/10.12701/yujm.2019.00150.
  40. Mortensen, J. K., & Andersen, G. (2021). Safety considerations for prescribing SSRI antidepressants to patients at increased cardiovascular risk. Expert Opinion on Drug Safety, 1–9. https://doi.org/10.1080/14740338.2022.1986001.
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