Drug-Induced Mania: Evidence and Precipitating Drugs

There is strong evidence that mania can be triggered by certain drugs, according to Peet (1995). These drugs include levodopa, corticosteroids, anabolic-androgenic steroids, and certain classes of antidepressants such as tricyclic and monoamine oxidase inhibitors.

Additionally, Peet (2012) suggests that there is weaker evidence that mania can be induced by dopaminergic anti-Parkinsonian drugs, thyroxine, iproniazid and isoniazid, sympathomimetic drugs, chloroquine, baclofen, alprazolam, captopril, amphetamine, and phencyclidine.

It is important for healthcare professionals to be aware of the potential for drug-induced mania and to monitor patients closely for any signs of symptoms. Patients should also be informed of the risks associated with these medications and advised to report any unusual changes in mood of behavior.

The liver is responsible for metabolizing valproate, and drugs that disrupt the CYP enzymes can greatly impact its levels. Valproic acid and semi-sodium valproate are approved for treating bipolar disorder, while sodium valproate is solely approved for epilepsy.

Valproate: Forms, Doses, and Adverse Effects

Valproate comes in three forms: semi-sodium valproate, valproic acid, and sodium valproate. Semi-sodium valproate is a mix of sodium valproate and valproic acid and is licensed for acute mania associated with bipolar disorder. Valproic acid is also licensed for acute mania, but this is not consistent with the Maudsley Guidelines. Sodium valproate is licensed for epilepsy. It is important to note that doses of sodium valproate and semi-sodium valproate are not the same, with a slightly higher dose required for sodium valproate.

Valproate is associated with many adverse effects, including nausea, tremor, liver injury, vomiting/diarrhea, gingival hyperplasia, memory impairment/confusional state, somnolence, weight gain, anaemia/thrombocytopenia, alopecia (with curly regrowth), severe liver damage, and pancreatitis. Increased liver enzymes are common, particularly at the beginning of therapy, and tend to be transient. Vomiting and diarrhea tend to occur at the start of treatment and remit after a few days. Severe liver damage is most likely to occur in the first six months of therapy, with the maximum risk being between two and twelve weeks. The risk also declines with advancing age.

Valproate is a teratogen and should not be initiated in women of childbearing potential. Approximately 10% of children exposed to valproate monotherapy during pregnancy suffer from congenital malformations, with the risk being dose-dependent. The most common malformations are neural tube defects, facial dysmorphism, cleft lip and palate, craniostenosis, cardiac, renal and urogenital defects, and limb defects. There is also a dose-dependent relationship between valproate and developmental delay, with approximately 30-40% of children exposed in utero experiencing delay in their early development, such as talking and walking later, lower intellectual abilities, poor language skills, and memory problems. There is also a thought to be a 3-fold increase of autism in children exposed in utero.

The three major types of learning are: operant conditioning, classical conditioning, and observational learning. In operant conditioning, an individual’s behavior is instrumental in achieving a desired outcome. In classical conditioning, a neutral stimulus is paired with a stimulus that already evokes a reflex response, eventually leading to the new stimulus evoking a similar response. Observational learning involves learning through the observation of others. Shaping, a part of operant conditioning, involves reinforcing successive approximations to a desired behavior. Extinction, seen in both classical and operant conditioning, involves the observed behavior gradually stopping due to the absence of reinforcement of presentation of the stimulus alone.

Water intoxication can cause polyuria and dilutional hyponatremia, but it does not typically lead to renal impairment. It is important to differentiate this condition from nephrogenic diabetes insipidus, which can develop in a significant percentage of patients on long-term lithium therapy and may present with nocturia as an early sign. While elevated calcium levels may occur in some patients on lithium, hyperparathyroidism is not a common clinical symptom. Tubulointerstitial nephritis is a rare complication of lithium therapy. The syndrome of inappropriate ADH secretion is not typically associated with polyuria of renal impairment and is not commonly linked to lithium therapy.

Amantadine and QTc Prolongation

Amantadine is a medication used to treat Parkinson’s disease and influenza. It has been associated with QTc prolongation, which can increase the risk of Torsades de points. Therefore, caution should be exercised when prescribing amantadine to patients with risk factors for QT prolongation. If a patient is already taking amantadine and develops a prolonged QTc interval, the medication should be discontinued and an alternative treatment considered. It is important to monitor the QTc interval in patients taking amantadine, especially those with risk factors for QT prolongation.

The working memory is overseen by the central executive, which manages all its functions. Although the exact location of the central executive is not fully comprehended, it is believed to involve various regions of the brain.

Memory Forms

Memory is the ability to store, retain, and retrieve information. There are different forms of memory, including sensory memory, short-term/working memory, and long-term memory.

Sensory memory is the capacity for briefly retaining the large amounts of information that people encounter daily. It includes echoic memory (gathered through auditory stimuli), iconic memory (gathered through sight), and haptic memory (acquired through touch).

Short-term memory is the ability to keep a small amount of information available for a short period of time. Atkinson and Shiffrin’s multistore model (1968) suggests the existence of a short-term storehouse with limited capacity. Baddeley and Hitch (1974) further developed the concept of short-term memory, which eventually became known as Baddeley’s multi-storehouse model (2000). This model includes the central executive, visuospatial sketchpad, phonological buffer/loop, and episodic buffer.

Long-term memory includes declarative (of explicit) memories, which can be consciously retrieved, and nondeclarative (of implicit) memories, which cannot. Declarative memory includes episodic memory (stores personal experiences) and semantic memory (stores information about facts and concepts). Non-declarative memory includes procedural memory (recalls motor and executive skills), associative memory (storage and retrieval of information through association with other information), and non-associative memory (refers to newly learned behavior through repeated exposure to an isolated stimulus).

Overall, memory is a complex and essential cognitive function that plays a crucial role in learning, reasoning, and understanding.

Inhibited Mania

Inhibited mania is one of the six mixed affective states identified by Kraepelin. It is characterized by symptoms of both mania and depression, but with a predominance of depressive features. Patients with inhibited mania may experience feelings of sadness, guilt, and worthlessness, as well as decreased energy and motivation. At the same time, they may also exhibit symptoms of mania, such as increased activity, impulsivity, and irritability.

Inhibited mania is considered an autonomous mixed episode, meaning that the patient consistently experiences symptoms of both mania and depression. This type of mixed state is associated with a poorer prognosis compared to those occurring between transitions from one mood state to another.

Treatment for inhibited mania typically involves a combination of mood stabilizers, antidepressants, and psychotherapy. It is important for clinicians to carefully monitor patients with inhibited mania, as they may be at increased risk for suicide and other adverse outcomes.

Depression (Brown and Harris)

In 1978, Brown and Harris conducted a study on 458 women in the inner London area of Camberwell to investigate the causes of depression. The study resulted in the development of a model that identified four vulnerability factors for depressive illness in women. These factors included having three of more children under the age of 14 at home, lacking an intimate relationship with a husband of boyfriend, lacking employment outside of the home, and experiencing the loss of a mother before the age of 11 years. The model emphasized the role of psychosocial factors in the development of depression.

Placebos that are inert can still cause negative effects.

Understanding the Placebo Effect

In general, a placebo is an inert substance that has no pharmacological activity but looks, smells, and tastes like the active drug it is compared to. The placebo effect is the observable improvement seen when a patient takes a placebo, which results from patient-related factors such as expectations rather than the placebo itself. Negative effects due to patient-related factors are termed the nocebo effect.

Active placebos are treatments with chemical activity that mimic the side effects of the drug being tested in a clinical trial. They are used to prevent unblinding of the drug versus the placebo control group. Placebos need not always be pharmacological and can be procedural, such as sham electroconvulsive therapy.

The placebo effect is influenced by factors such as the perceived strength of the treatment, the status of the treating professional, and the branding of the compound. The placebo response is greater in mild illness, and the response rate is increasing over time. Placebo response is usually short-lived, and repeated use can lead to a diminished effect, known as placebo sag.

It is difficult to separate placebo effects from spontaneous remission, and patients who enter clinical trials generally do so when acutely unwell, making it challenging to show treatment effects. Breaking the blind may influence the outcome, and the expectancy effect may explain why active placebos are more effective than inert placebos. Overall, understanding the placebo effect is crucial in clinical trials and personalized medicine.

The examiner’s use of minimal force to move the patient’s arm is an instance of automatic obedience, but it can be categorized more precisely as mitgehen, which represents a heightened form of automatic obedience.

– Catatonia is a psychiatric syndrome characterized by disturbed motor functions, mood, and thought.
– Key behaviors associated with catatonia include stupor, posturing, waxy flexibility, negativism, automatic obedience, mitmachen, mitgehen, ambitendency, psychological pillow, forced grasping, obstruction, echopraxia, aversion, mannerisms, stereotypies, motor perseveration, echolalia, and logorrhoea.
– These behaviors are often tested in exam questions.
– Karl Ludwig Kahlbaum is credited with the original clinical description of catatonia.

The ascent of the National Socialist Party during the 1930s had a negative effect on psychiatry in Germany, which was previously a leading force in European psychiatry. As a result of the Second World War, numerous skilled scientists and psychiatrists fled Germany and sought refuge in the United States. Their contributions were instrumental in establishing the US as the dominant force in both academic and clinical psychiatry.

The biological response to a drug can only be triggered by the portion of the drug that is not bound.

Drug Distribution in the Body

After being absorbed, drugs can distribute to different parts of the body, such as fat, plasma, muscle, brain tissue, and glands like the thyroid. However, for a drug to have an effect, it must be present in the plasma in an unbound state. This means that the drug molecules are not attached to any other molecules and are free to interact with their target receptors. The concentration of unbound drug in the plasma is what determines the drug’s effectiveness and potential side effects. Therefore, understanding a drug’s distribution in the body is crucial for determining the appropriate dosage and monitoring its effects.

The use of cholinesterase inhibitors may worsen behaviour in individuals with frontotemporal dementia. However, these inhibitors are approved for treating Alzheimer’s dementia and Parkinson’s disease dementia (rivastigmine). While NICE guidelines do not recommend their use for non-cognitive symptoms in dementia with Lewy bodies, they can be prescribed for mixed dementia with a primary Alzheimer’s pathology.

Acute stress disorder is a brief yet intense condition triggered by a highly distressing event that can cause a range of symptoms. Although the symptoms can appear quickly, they typically subside within a few days. These symptoms may include psychological effects like feeling disconnected of confused, as well as physical symptoms such as sweating, trembling, heart palpitations, and difficulty sleeping. In some cases, individuals may progress to develop post-traumatic stress disorder.

Post-traumatic stress disorder (PTSD) is a condition that develops in response to an exceptionally threatening of catastrophic event of situation, such as the one described above. It is only diagnosed if symptoms arise within six months of the traumatic event. The symptoms of PTSD can be categorized into three groups: re-experiencing the traumatic event (such as through nightmares of vivid thoughts), persistent avoidance of stimuli associated with the trauma, and persistent symptoms of increased arousal (such as difficulty sleeping of concentrating).

Agoraphobia is a fear of being in situations of places from which escape is difficult, leading to avoidance of many situations and confinement to the home. This fear is typically triggered by situations such as crowds, public places, of traveling alone of away from home.

Generalized anxiety disorder is characterized by persistent anxiety that is not limited to any specific environmental circumstance. To receive this diagnosis, a patient must experience symptoms of anxiety on most days for several weeks of months, with evidence of impairment in important areas of functioning. However, this diagnosis is not appropriate for the scenario described above, as the anxiety is related to a specific event of trigger.

Panic disorder involves sudden onset of severe anxiety, with at least three panic attacks experienced over a three-week period. Symptoms may include sweating, palpitations, shortness of breath, nausea, trembling, chest pain of discomfort, dizziness of lightheadedness, chills of hot flushes, fear of losing control of dying, paraesthesia, feeling of choking, and derealization or depersonalization.

Social phobia is characterized by a marked fear of social situations in which embarrassment may occur, leading to avoidance of these situations.

First Rank Symptoms: Their Significance in Identifying Schizophrenia

First rank symptoms were introduced by Kurt Schneider in 1938 as a practical tool for non-psychiatrists to identify schizophrenia. While they are highly suggestive of schizophrenia, they are not pathognomonic and can also be seen in affective and personality disorders. Additionally, there is no evidence to support their prognostic significance.

A systematic review in 2015 found that first rank symptoms differentiated schizophrenia from nonpsychotic mental health disorders with a sensitivity of 61.8% and a specificity of 94.1%. They also differentiated schizophrenia from other types of psychosis with a sensitivity of 58% and a specificity of 74.7%.

The first rank symptoms include running commentary, thought echo, voices heard arguing, thought insertion, thought withdrawal, thought broadcast, delusional perception, somatic passivity, made affect, and made volition. While they can be helpful in identifying schizophrenia, they should not be relied upon as the sole diagnostic criteria.

Passivity Phenomena in a Patient: An Example

The patient in question experiences the sensation of an external force attempting to interfere with his thoughts and actions. This is an example of passivity phenomena. Although he holds a belief in black magic, this may be considered a secondary delusional belief. The patient may also exhibit formal thought disorder, but the combination of thought passivity and the belief in external influence is more consistent with an overall description of passivity phenomena.

While overvalued ideas can interfere with normal social functioning, they may be considered culturally appropriate to a lesser degree. However, the nature of the patient’s experiences precludes this possibility. There is no evidence of pseudo of other hallucinatory experiences.

Attachment Theory and Harlow’s Monkeys

Attachment theory, developed by John Bowlby, suggests that children have an innate tendency to form relationships with people around them to increase their chance of survival. This attachment is different from bonding, which concerns the mother’s feelings for her infant. Children typically single out a primary caregiver, referred to as the principle attachment figure, from about 1-3 months. The quality of a person’s early attachments is associated with their adult behavior, with poor attachments leading to withdrawn individuals who struggle to form relationships and good attachments leading to socially competent adults who can form healthy relationships.

Bowlby’s attachment model has four stages: preattachment, attachment in the making, clear-cut attachment, and formation of reciprocal attachment. The time from 6 months to 36 months is known as the critical period, during which a child is most vulnerable to interruptions in its attachment. Attachments are divided into secure and insecure types, with insecure types further divided into avoidant and ambivalent types.

Harlow’s experiment with young rhesus monkeys demonstrated the importance of the need for closeness over food. The experiment involved giving the monkeys a choice between two different mothers, one made of soft terry cloth but provided no food and the other made of wire but provided food from an attached baby bottle. The baby monkeys spent significantly more time with their cloth mother than with their wire mother, showing the importance of attachment and closeness in early development.

Modafinil: A Psychostimulant for Wakefulness and Attention Enhancement

Modafinil is a type of psychostimulant that is known to improve wakefulness, attention, and vigilance. Although it is similar to amphetamines, it does not produce the same euphoric effects and is not associated with dependence of tolerance. Additionally, it does not seem to cause psychosis. Modafinil is approved for the treatment of narcolepsy, obstructive sleep apnea, and chronic shift work. It is also suggested as an adjunctive treatment for depression by the Maudsley. Recently, it has gained popularity as a smart drug due to its potential to enhance cognitive functioning in healthy individuals.

The Role of the Ventral Tegmental Area in Reward and Pleasure

The midbrain contains a cluster of dopaminergic cells known as the ventral tegmental area (VTA), which plays a crucial role in the experience of reward and pleasure. These cells are involved in the release of dopamine, a neurotransmitter that is associated with feelings of pleasure and motivation. The VTA is activated in response to various stimuli, such as food, sex, and drugs, and is responsible for the pleasurable sensations that accompany these experiences. Dysfunction in the VTA has been linked to addiction and other disorders related to reward processing. Understanding the role of the VTA in reward and pleasure is essential for developing effective treatments for these conditions.

Recent clinical trials have shown that various psychotherapy approaches do not differ significantly in terms of effectiveness. This particular trial aimed to prove that psychodynamic psychotherapy was not inferior to other modalities at 22 weeks and one year follow-up. While non-inferiority was observed at 22 weeks, it could not be conclusively demonstrated at one year, despite no significant difference between interventions. Interestingly, individuals who received CBT appeared to require more additional treatment during the year following therapy, although this trend was not statistically significant.

Lithium is known to cause hypercalcemia and hyperparathyroidism, which can lead to various symptoms. These symptoms may include constipation (groans), kidney stones (stones), bone pain (bones), and mental health issues such as depression, lethargy, and confusion (psychic moans).

Lithium – Pharmacology

Pharmacokinetics:
Lithium salts are rapidly absorbed following oral administration and are almost exclusively excreted by the kidneys unchanged. Blood samples for lithium should be taken 12 hours post-dose.

Ebstein’s:
Ebstein’s anomaly is a congenital malformation consisting of a prolapse of the tricuspid valve into the right ventricle. It occurs in 1:20,000 of the general population. Initial data suggested it was more common in those using lithium but this had not held to be true.

Contraindications:
Addison’s disease, Brugada syndrome, cardiac disease associated with rhythm disorders, clinically significant renal impairment, untreated of untreatable hypothyroidism, low sodium levels.

Side-effects:
Common side effects include nausea, tremor, polyuria/polydipsia, rash/dermatitis, blurred vision, dizziness, decreased appetite, drowsiness, metallic taste, and diarrhea. Side-effects are often dose-related.

Long-term use is associated with hypothyroidism, hyperthyroidism, hypercalcemia/hyperparathyroidism, irreversible nephrogenic diabetes insipidus, and reduced GFR.

Lithium-induced diabetes insipidus:
Treatment options include stopping lithium (if feasible), keeping levels within 0.4-0.8 mmol/L, once-daily dose of the drug taken at bedtime, amiloride, thiazide diuretics, indomethacin, and desmopressin.

Toxicity:
Lithium salts have a narrow therapeutic/toxic ratio. Risk factors for lithium toxicity include drugs altering renal function, decreased circulating volume, infections, fever, decreased oral intake of water, renal insufficiency, and nephrogenic diabetes insipidus. Features of lithium toxicity include GI symptoms and neuro symptoms.

Pre-prescribing:
Before prescribing lithium, renal function, cardiac function, thyroid function, FBC, and BMI should be checked. Women of childbearing age should be advised regarding contraception, and information about toxicity should be provided.

Monitoring:
Lithium blood levels should be checked weekly until stable, and then every 3-6 months once stable. Thyroid and renal function should be checked every 6 months. Patients should be issued with an information booklet, alert card, and record book.

The serum concentration of valproic acid may be elevated by chlorpromazine, although the reason for this is not fully understood. However, this outcome is widely acknowledged.

Chlorpromazine: Photosensitivity Reactions and Patient Precautions

Chlorpromazine, the first drug used for psychosis, is a common topic in exams. However, it is important to note that photosensitivity reactions are a known side effect of its use. Patients taking chlorpromazine should be informed of this and advised to take necessary precautions. Proper education and awareness can help prevent potential harm from photosensitivity reactions.

Serotonin Syndrome and Neuroleptic Malignant Syndrome are two conditions that can be difficult to differentiate. Serotonin Syndrome is caused by excess serotonergic activity in the CNS and is characterized by neuromuscular abnormalities, altered mental state, and autonomic dysfunction. On the other hand, Neuroleptic Malignant Syndrome is a rare acute disorder of thermoregulation and neuromotor control that is almost exclusively caused by antipsychotics. The symptoms of both syndromes can overlap, but there are some distinguishing clinical features. Hyper-reflexia, ocular clonus, and tremors are more prominent in Serotonin Syndrome, while Neuroleptic Malignant Syndrome is characterized by uniform ‘lead-pipe’ rigidity and hyporeflexia. Symptoms of Serotonin Syndrome usually resolve within a few days of stopping the medication, while Neuroleptic Malignant Syndrome can take up to 14 days to remit with appropriate treatment. The following table provides a useful guide to the main differentials of Serotonin Syndrome and Neuroleptic Malignant Syndrome.

Alternative Routes of Administration for Antidepressants

While most antidepressants are taken orally, there are a few alternative routes of administration available. However, it is important to note that these non-oral preparations should only be used when absolutely necessary, as they may not have a UK licence.

One effective alternative route is sublingual administration of fluoxetine liquid. Buccal administration of selegiline is also available. Crushed amitriptyline has been shown to be effective when administered via this route.

Intravenous administration is another option, with several antidepressants available in IV preparations, including citalopram, escitalopram, mirtazapine, amitriptyline, clomipramine, and allopregnanolone (which is licensed in the US for postpartum depression). Ketamine has also been shown to be effective when administered intravenously.

Intramuscular administration of flupentixol has been shown to have a mood elevating effect, but amitriptyline was discontinued as an IM preparation due to the high volumes required.

Transdermal administration of selegiline is available, and suppositories containing amitriptyline, clomipramine, imipramine, and trazodone have been manufactured by pharmacies, although there is no clear data on their effectiveness. Sertraline tablets and doxepin capsules have also been given rectally.

As the concentration decreases, the half-life of a zero order reaction becomes shorter. This is because zero order kinetics involve constant elimination, meaning that the rate of elimination does not change with increasing concentration. Therefore, as the concentration decreases, there is less drug available to be eliminated at a constant rate, resulting in a shorter half-life.

The half-life of a drug is the time taken for its concentration to fall to one half of its value. Drugs with long half-lives may require a loading dose to achieve therapeutic plasma concentrations rapidly. It takes about 4.5 half-lives to reach steady state plasma levels. Most drugs follow first order kinetics, where a constant fraction of the drug in the body is eliminated per unit time. However, some drugs may follow zero order kinetics, where the plasma concentration of the drug decreases at a constant rate, despite the concentration of the drug. For drugs with nonlinear kinetics of dose-dependent kinetics, the relationship between the AUC of CSS and dose is not linear, and the kinetic parameters may vary depending on the administered dose.

Assessment and Management of Obesity

Obesity is a condition that can increase the risk of various health problems, including type 2 diabetes, coronary heart disease, some types of cancer, and stroke. The body mass index (BMI) is a commonly used tool to assess obesity, calculated by dividing a person’s weight in kilograms by their height in meters squared. For adults over 20 years old, BMI falls into one of the following categories: underweight, normal of healthy weight, pre-obesity/overweight, obesity class I, obesity class II, and obesity class III.

Waist circumference can also be used in combination with BMI to guide interventions. Diet and exercise are the main interventions up to a BMI of 35, unless there are comorbidities such as type 2 diabetes, hypertension, cardiovascular disease, osteoarthritis, dyslipidemia, and sleep apnea. Physical activity recommendations suggest that adults should accumulate at least 150 minutes of moderate intensity activity of 75 minutes of vigorous intensity activity per week. Dietary recommendations suggest diets that have a 600 kcal/day deficit.

Pharmacological options such as Orlistat of Liraglutide may be considered for those with a BMI of 30 kg/m2 of more, of 28 if associated risk factors. Surgical options such as bariatric surgery may be considered for those with a BMI of 40 kg/m2 of more, of between 35 kg/m2 and 40 kg/m2 with other significant diseases that could be improved with weight loss.

Pharmacokinetics is the study of how drugs are affected by the body. This includes how drugs are absorbed into the bloodstream, distributed throughout the body, metabolized into different forms, and eliminated from the body. The acronym ADME is often used to remember these processes. Absorption refers to the transportation of the drug from the site of administration to the bloodstream. Hydrophobic drugs are absorbed better than hydrophilic ones. Distribution refers to the movement of the drug from the bloodstream to other areas of the body. Metabolism involves the conversion of the drug into different forms, often to make it more easily excreted by the kidneys. This process occurs in two phases, involving reduction of hydrolysis in phase 1 and conjugation in phase 2. Excretion refers to the elimination of the drug from the body, which mainly occurs through the kidneys and biliary system.

Agoraphobia is the most probable diagnosis, even though not all individuals with agoraphobia experience panic attacks.

Genomic Imprinting and its Role in Psychiatric Disorders

Genomic imprinting is a phenomenon where a piece of DNA behaves differently depending on whether it is inherited from the mother of the father. This is because DNA sequences are marked of imprinted in the ovaries and testes, which affects their expression. In psychiatry, two classic examples of genomic imprinting disorders are Prader-Willi and Angelman syndrome.

Prader-Willi syndrome is caused by a deletion of chromosome 15q when inherited from the father. This disorder is characterized by hypotonia, short stature, polyphagia, obesity, small gonads, and mild mental retardation. On the other hand, Angelman syndrome, also known as Happy Puppet syndrome, is caused by a deletion of 15q when inherited from the mother. This disorder is characterized by an unusually happy demeanor, developmental delay, seizures, sleep disturbance, and jerky hand movements.

Overall, genomic imprinting plays a crucial role in the development of psychiatric disorders. Understanding the mechanisms behind genomic imprinting can help in the diagnosis and treatment of these disorders.