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Abstract: Sustained response versus relapse: the pharmacotherapeutic goal for OCD

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posted Monday, 8 October 2007

Int Clin Psychopharmacol. 2007 Nov; 22(6): 313-322;

Sustained response versus relapse: the pharmacotherapeutic goal for obsessive-compulsive disorder.

Fineberg NA, Pampaloni I, Pallanti S, Ipser J, Stein. DJ

Convincing evidence from placebo-referenced randomized controlled trials supports efficacy for clomipramine and selective serotonin reuptake inhibitors for acute treatment of obsessive-compulsive disorder. It remains less conclusively understood whether these agents maintain efficacy over the longer term. This paper systematically reviews long-term medication studies in obsessive-compulsive disorder.

Studies of clomipramine, fluoxetine and sertraline investigated 'responders' from acute treatment trials and extended treatment up to 12 months versus placebo. Responses to medication were sustained.

A 24-week placebo-controlled trial of escitalopram (10 mg or 20 mg/day) and paroxetine (40 mg/day) demonstrated ongoing efficacy for all three treatments. Studies that randomized treated cases to placebo demonstrated reemergence of symptoms in the placebo-treated cohort.

Six relapse prevention trials were found by systematic search. Some, but not all, revealed significant advantages for remaining on medication. Paroxetine (20-60 mg/day) and escitalopram (10 or 20 mg/day) were each found to outperform placebo in preventing relapse during 24 weeks of double-blind, randomized follow-up.

Meta-analysis, using Review Manager software (4.2.8), detected overall superiority of selective serotonin reuptake inhibitors to placebo in preventing relapse among adult treatment-responders. Worsening by five Yale-Brown Obsessive Compulsive Scale points emerged from the review as a suggested threshold for relapse.

Viewed collectively, these results suggest that selective serotonin reuptake inhibitors are effective long-term treatments and relapse prevention represents the treatment target for obsessive-compulsive disorder.

(Text has been reformatted for clarity; ed.)

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Action-potential

Wave of electrochemical activity generated by the flow of positively charged ions across the neuronal membrane which causes a neuron to 'fire'
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Affective disorders

Mental disorders characterized by dramatic changes or extremes of mood - depression, mania, or both - including depression, bipolar disorder (manic depression), and schizo affective disorders.
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Alleles

An alternative form of a gene (one member of a pair) that is located at a specific position on a specific chromosome. There are two alleles for each trait.
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Amygdalae

Two almond-shaped groups of neurons - there is one amygdala (Greek for almond) in each brain hemisphere. They have the primary role in processing and storing memories of emotional reactions.

Part of the Limbic System the amygdalae trigger an instant fear reaction to perceived threats, real or imagined.
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Anterior cingulate cortex

Has a role in empathy, emotions, cognitive control (attention, conflict monitoring during information processing) and plays a role in stimulus reinforcement learning and reward-guided selection of actions.

Also controls autonomic functions such as heart rate and blood pressure in the context of current behavior.
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Brain-derived neurotrophic factor

Protein required for the growth and survival of nerve cells during development, and for maintenance of adult nerve cells. Studies have shown that some neurotrophic factors can trigger regrowth of damaged nerve cells and stimulate growth and differentiation of new neurons and synapses in the hippocampus.
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Cognitive-behavior therapy (CBT)

Type of psychotherapy emphasizing the important role of thinking in how we feel and what we do.

Based on the concept that our thoughts cause our feelings and behaviors, not external things like people, situations, and events. The benefit of this fact is that we can change the way we think to feel/act better even if the situation does not change.
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Clinical trial-Phase 1

The first test in humans of a new treatment to see if it is safe to use in people.
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Compassion meditation

Based on Tibetan Buddhism techniques. Trains the mind to optimize the way it perceives relationships with others. Experienced practitioners are able to alter brain functioning to boost positive emotions, and enhance their immune systems.

Related to Mindfulness Meditation/Psychotherapy.
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Corticotropin-releasing factor

A polypeptide hormone and neuro- transmitter involved in the stress response.

CRF hyper secretion is believed to contribute to hyperactivity of the hypothalamic-pituitary-adrenal axis in depressed patients. Hyper secretion has also been implicated in anxiety.
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Cortisol

The most potent of the stress hormones. Synthesized from cholesterol by the adrenal glands. Increases blood pressure, blood sugar levels and suppresses immune function.
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Dentate gyrus

Part of the hippocampus. Thought to contribute to formation of new memories and is one of the few brain regions where neurogenesis occurs. Has a role in recognizing the differences that make each place unique. Processing errors may play a role in deja vu.
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Depression - Atypical

Defined by the ability to feel better temporarily in response to positive life events, plus any two of the following criteria: excessive sleep, overeating, a feeling of heaviness in the limbs and a sensitivity to rejection. Despite the name, it is actually the most common form of depression.
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Depression - Clinical/Major

Characterized by a pervasive, unremitting low mood and loss of interest or pleasure in usual activities. In addition there are other physical and mental symptoms that may include fatigue, difficulty with concentration and memory, feelings of hopelessness and helplessness, headaches, body aches, and thoughts of suicide.
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Epigenetics

Process by which environmental factors like diet, stress, and ante/post-natal maternal factors can change gene function without altering the DNA sequence. These changes may remain through cell divisions and may also be passed down through multiple generations.
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First-degree relative

A parent, sibling or child of an individual.

Gamma-Aminobutyric Acid (GABA)

The major inhibitory neurotransmitter of the central nervous system. Dampens brain activity and promotes a state of calm.

An amino acid produced in the brain as a by-product of the Krebs glucose metabolism cycle which powers brain cells.

Note 1: Benzodiazepines (Valium® etc) do not increase brain GABA levels, but increase the sensitivity of GABA receptors.

Note 2: GABA does not penetrate the Brain-Blood-Barrier so GABA supplements are, at best, expensive placebos.
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Heterozygote, Homozygote

Heterozygote: Any organism which has two differing forms of a particular gene for a specific trait, one inherited from each parent.

Homozygote: Any organism which has two identical forms of a particular gene for a specific trait, one inherited from each parent.

Because genes are either dominant or recessive, the genetic makeup (genotype) of an organism cannot always be determined by physical appearance alone.

Hippocampus

A seahorse shaped sheet of neurons laying next to the Amygdalae. Regulates emotions and short term memory.
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Homologous

Anatomical structures that perform the same function in different biological species having evolved from the same structure in a shared ancestor species.

Hypothalamus

Regulates homeostasis, the maintenance of the body's status quo by producing hormones which control: Body temperature, Hunger, Moods, Sex drive, Sleep and Thirst.
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Interpersonal psychotherapy

Time-limited psychotherapy focusing on the interpersonal context and building interpersonal skills. Based on the belief that interpersonal factors may contribute heavily to psychological problems. Distinguished from other forms of therapy in its emphasis on the interpersonal rather than the intra psychic.
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Lyme disease

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In addition to symptoms typical of infectious disease - fever, chills, headache, rash etc, Lyme can also produce 'classic' anxiety symptoms including tingling or numbness of the extremities, disorientation, mental 'fog,' short term memory loss, fatigue, poor concentration and sleep disturbance, and may trigger depression. In some cases, these symptoms may not become apparent for many years after the initial infection.
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Meta-analysis

Mathematical technique to amalgamating, summarizing, and reviewing previous quantitative research to arrive at one overall measure of treatment effect.

A weakness of the method is that sources of bias in the original research are not controlled by the method. A good meta-analysis of badly designed studies will still result in bad statistics.
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Mindfulness psychotherapy

Mindfulness is the practice of becoming more aware of the present moment, rather than dwelling in the past or projecting into the future. It generally involves a heightened awareness of sensory stimuli (really noticing your breathing, feeling the sensations of your body, etc); and being 'in the now'. Principles may be combined with the concepts of Cognitive-Behavior Therapy (CBT) as Mindfulness-based Psychotherapy.
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Neurogenesis

Process by which new neurons are generated after the postnatal stage of development. It appears to only occur in two areas of the brain, the hippocampus and the olfactory bulbs. Hippocampal neurogenesis is thought to counter anxiety and depression.
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Neuropeptide

One of about 100 peptides including endorphins, enkephalins, oxytocin and vasopressin which mediate brain function by regulating gene expression, local blood flow and synaptogenesis. The neuropeptides Cholecystokinin, Substance P and Neuropeptide Y have been linked to anxiety and depressive disorders.
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Neuroplastic

The brain's ability to reorganize itself by forming new neural connections.
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Polymorphism

Natural variations in a gene, DNA sequence, protein, or chromosome-Click page link for more information-

Prefrontal Cortex

Area of the brain's frontal lobes involved in planning complex cognitive behaviors, the expression of personality and social behavior.
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Prospective study

Tests a specific question, usually about how a specific exposure(s) affects a specific outcome(s) by recruiting appropriate participants and checks the outcomes over the following months or years.

Psychodynamic psychotherapy

Talking therapy used to help a person find relief from emotional pain. It is based on the theories and techniques of Freudian/Jung style psychoanalysis. However, practitioners don't necessarily accept the 'classical' psychoanalysis theory that emotional conflicts are primarily sexual in nature.

Receptor

Short-lived protein molecules embedded in the cell wall of neurons, especially of their synapses, to which neurotransmitters attach to initiate an action. Also called ´binding sites´
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Receptor agonist

A chemical which is able to bind to receptors of a neurotransmitter and trigger the same biological response as that neurotransmitter.

Receptor antagonist

A drug that is so similar chemically to a neurotransmitter that it is capable of binding to a receptor for the neurotransmitter but which does not trigger the biological response of that neurotransmitter. By blocking its receptors the antagonist disrupts or inhibits the action of the neurotransmitter.

Seasonal affective disorder

A type of depression triggered by the seasons. The most common type is winter-onset depression (aka Winter blues), but some also regularly become depressed at the start of spring-summer.
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Serotonin transporter

A protein that transports the neurotransmitter serotonin across cell membranes.
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Somatization disorder

Manifests as chronic, persistent complaints of varied physical symptoms that have no identifiable organic origin or basis. Often co morbid with other psychological disorders, particularly anxiety or mood disorders, plus irritable bowel syndrome and chronic pain. Occurs in 0.2% to 2% of females and 0.2% of males. Also known as Briquet's disorder.-Click page link for more information-

Sympathetic nervous system

The part of the nervous system which controls the body’s internal, involuntary processes including breathing, digestion, blood vessel tone, heart rate, etc. It also mediates the fight-or-flight response.

Synapses

Gaps between neurons through which "information" flows from one neuron (brain cell) to another.
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White matter

Regions of the brain and spinal cord largely composed of nerve fibers (axons) sheathed in insulating myelin composed of lipids (fats) which give them their color.

White matter abnormalities (hyperintensities):
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